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Publication numberUS7541357 B2
Publication typeGrant
Application numberUS 11/183,066
Publication dateJun 2, 2009
Filing dateJul 15, 2005
Priority dateJul 15, 2004
Fee statusPaid
Also published asCA2573271A1, CN101119969A, CN101119969B, CN103880827A, EP1778639A2, EP1778639A4, US8227486, US8236796, US8741901, US20060052378, US20060063766, US20090048443, US20090253906, US20130005965, US20140243524, WO2006020049A2, WO2006020049A3, WO2006020049A8
Publication number11183066, 183066, US 7541357 B2, US 7541357B2, US-B2-7541357, US7541357 B2, US7541357B2
InventorsBruce F. Molino, Shuang Liu, Peter R. GUZZO, James P. Beck
Original AssigneeAmr Technology, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
US 7541357 B2
Abstract
The compounds of the present invention are represented by the chemical structure found in Formula (I):

wherein:
  • the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined in R14;
  • with R1, R2, R3, R4, R5, R6, R7, R8, and R14 defined herein.
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Claims(37)
1. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is methyl, ethyl, or isopropyl;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1, wherein R1 is methyl.
3. The compound according to claim 1, wherein R1 is ethyl or isopropyl.
4. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is methyl or gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
5. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is methyl, hydroxy, methoxy, fluoro, or chloro;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 5, wherein R3 is hydroxy or methoxy.
7. The compound according to claim 5, wherein R3 is fluoro or chloro.
8. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is phenyl optionally and independently substituted from 1 to 4 times with R14; or
R4 is naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles, optionally substituted from 1 to 4 times with R14; or
R4is CH3, OH, or OCH3; or
R4 F, Cl, or —CN; or
R4 selected from the group consisting of morpholin-4-yl, 2,6-dimethyl-morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, [1,2]oxazinan-2-yl, isoxazolidin-2-yl, morpholin-4-ylmethyl, 1-methyl-1-morpholin-4-ylethyl, 1-morpholin-4-yl-cyclopropyl, piperidin-1-ylmethyl, pyrrolidin-1-ylmethyl, dimethylaminomethyl, 1-dimethylamino-1-methylethyl, 1-dimethylamino-cyclopropyl, methylaminomethyl, 1-methyl-1-methylaminoethyl, 1-methylamino-cyclopropyl, aminomethyl, 1-amino-1-methylethyl, 1-aminocyclopropyl, and methanesulfonyl;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
9. The compound according to claim 8, wherein R4 is naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles, optionally substituted from 1 to 4 times with R14.
10. The compound according to claim 9, wherein R4 is selected from the group consisting of 3,5-dimethyl-isoxazol-4-yl, pyrazol-1-yl, 3,5-dimethyl-1H-pyrazol-4-yl, 1,3,5-trimethyl-1H-pyrazol-4-yl, pyridin-2-yl, 3-methyoxy-pyridin-2-yl, 4-methoxy-pyridin-2-yl, 3-methyl-pyridin-2-yl, 4-methyl-pyridin-2-yl, 6-methyoxy-pyridin-2-yl, pyridin-3-yl, 2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, pyridin-4-yl, pyrimidin-4-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazin-2-yl, 3-methyl-pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-methyl-pyrazin-2-yl, 3-methoxy-pyrazin-2-yl, 5-methoxy-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-ethyl-pyrazin-2-yl, 6-trifluoromethyl-pyrazin-2-yl, pyridazin-3-yl, 5-methylpyridazin-3-yl, 6-methylpyridazin-3-yl, 6-dimethylamino-pyridazin-3-yl, 6-methylamino-pyridazin-3-yl, 6-amino-pyridazin-3-yl, 6-morpholin-4-yl-pyridazin-3-yl, 6-trifluoromethyl-pyridazin-3-yl, 6-cyano-pyridazin-3-yl, pyridazin-4-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, [1,3,5]triazin-2-yl, [1,2,4]triazin-3-yl, [1,2,4]triazin-5-yl, [1,2,4]triazin-6-yl, cinnolin-3-yl, phthalazin- l-yl, phthalazin-6-yl, quinoxalin-2-yl, quinoxalin-6-yl, quinazolin-2-yl, quinazolin-4-yl, quinazolin-6-yl, quinazolin-7-yl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2-yl, and 2-oxo-2H-pyridin-1-yl.
11. The compound according to claim 10, wherein R4 is selected from the group consisting of 3,5-dimethyl-isoxazol-4-yl, pyrazol-1-yl, 3,5-dimethyl-1H-pyrazol-4-yl, 1,3,5-trimethyl-1H-pyrazol-4-yl, pyridin-2-yl, 3-methyoxy-pyridin-2-yl, 4-methoxy-pyridin-2-yl, 3-methyl-pyridin-2-yl, 4-methyl-pyridin-2-yl, 6-methyoxy-pyridin-2-yl, pyridin-3-yl, 2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, pyridin-4-yl, pyrimidin-4-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazin-2-yl, 3-methyl-pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-methyl-pyrazin-2-yl, 3-methoxy-pyrazin-2-yl, 5-methoxy-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-ethyl-pyrazin-2-yl, 6-trifluoromethyl-pyrazin-2-yl, pyridazin-3-yl, 6-methylpyridazin-3-yl, 6-dimethylamino-pyridazin-3-yl, 6-methylamino-pyridazin-3-yl, 6-amino-pyridazin-3-yl, 6-morpholin-4-yl-pyridazin-3-yl, 6-trifluoromethyl-pyridazin-3-yl, 6-cyano-pyridazin-3-yl, and pyridazin-4-yl.
12. The compound according to claim 10, wherein R4 is selected from the group consisting of pyrimidin-4-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazin-2-yl, 3-methyl-pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-methyl-pyrazin-2-yl, 3-methoxy-pyrazin-2-yl, 5-methoxy-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-ethyl-pyrazin-2-yl, 6-trifluoromethyl-pyrazin-2-yl, pyridazin-3-yl, 6-methylpyridazin-3-yl, 6-dimethylamino-pyridazine-3-yl, 6-methylamino-pyridazine-3-yl, 6-amino-pyridazine-3-yl, 6-morpholin-4-yl-pyridazine-3-yl, 6-trifluoromethyl-pyridazin-3-yl, 6-cyano-pyridazin-3-yl, and pyridazin-4-yl.
13. The compound according to claim 8, wherein R4 is CH3, OH, or OCH3.
14. The compound according to claim 8, wherein R4 is F, Cl or —CN.
15. The compound according to claim 8, wherein R4 is selected from the group consisting of morpholin-4-yl, 2,6-dimethyl-morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, [1,2]oxazinan-2-yl, isoxazolidin-2-yl, morpholin-4-ylmethyl, 1-methyl-1-morpholin-4-ylethyl, 1-morpholin-4-yl-cyclopropyl, piperidin-1-ylmethyl, pyrrolidin-1-ylmethyl, dimethylaminomethyl, 1-dimethylamino-1-methylethyl, 1-dimethylamino-cyclopropyl, methylaminomethyl, 1-methyl-1-methylaminoethyl, 1-methylamino-cyclopropyl, aminomethyl, 1-amino-1-methylethyl, 1-aminocyclopropyl, and methanesulfonyl.
16. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 is H, halogen, or C1-C6 alkyl;
R6 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl:
R8 is H, halogen —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
17. The compound according to claim 16, wherein R5 is CH3.
18. The compound according to claim 16, wherein R5 is F or Cl.
19. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is CH3 or gem-dimethyl;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
20. The compound according to claim 16, wherein
R1 is methyl, ethyl, or isopropyl;
R2 is H, CH3, or gem-dimethyl;
R3 is H, CH3, OH, OCH3, —CN, or F;
R4 is H, CH3, OH, OCH3—CN, or F;
R5 is H or F;
R6 is H, F, or methoxy;
R7 is H;
R8 is H, OH, OCH3, —CN, F, Cl, or CH3; and
X is selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, chromenyl, indenyl, indanyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted from 1 to 4 times with R14.
21. The compound according to claim 16, wherein the compound is 4-(1H-inden-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline or 4-(indan-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline.
22. The compound according to claim 16, wherein:
R1 is methyl, ethyl, or isopropyl;
R2 is H, CH3, or gem-dimethyl;
R3 is H, CH3, OH, OCH3, —CN, or F;
R4 is H, CH3, OH, OCH3—CN, or F;
R5 is H or F;
R6 is H, F, or methoxy;
R7 is H;
R8 is H, OH, OCH3, CN, F, Cl, or CH3; and
X is selected from the group consisting of naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, dihydrobenzocycloheptenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted from 1 to 4 times with R14.
23. The compound according to claim 2, wherein X is naphthalen-1-yl, 4-methyl-naphthalen-1-yl, naphthalen-2-yl, 1-fluoro-naphthalen-2-yl, 1-chloro-naphthalen-2-yl, 1-methoxy-naphthalen-2-yl, 1-methyl-naphthalen-2-yl, 3-fluoro-naphthalen-2-yl, 3-chloro-naphthalen-2-yl, 3-methoxy-naphthalen-2-yl, 3-cyano-naphthalen-2-yl, 4-fluoro-naphthalen-2-yl, 4-chloro-naphthalen-2-yl, 4-methyl-naphthalen-1-yl, 5-fluoro-naphthalen-2-yl, 5-chloro-naphthalen-2-yl, 5-cyano-naphthalen-2-yl, 5-methyl-naphthalen-2-yl, 6-methoxy-naphthalen-2-yl, 6-chloro-naphthalen-2-yl, 6-fluoro-naphthalen-2-yl, 6-cyano-naphthalen-2-yl, 6-methanesulfonyl-naphthalen-2-yl, 7-methoxy-naphthalen-2-yl, 7-chloro-naphthalen-2-yl, 7-fluoro-naphthalen-2-yl, 7-cyano-naphthalen-2-yl, 8-methoxy-naphthalen-2-yl, 8-chloro-naphthalen-2-yl, 8-fluoro-naphthalen-2-yl, 8-cyano-naphthalen-2-yl, 8-methoxy-naphthalen-2-yl, 5,6,7,8-tetrahydro-naphthalen-2-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, 2-quinoxalinyl, 6-quinoxalinyl, 2-quinazolinyl, 2-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 3-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 6-phthalazinyl, 2H-chromen-3-yl, or 8,9-dihydro-7H-benzocyclohepten-6-yl.
24. The compound according to claim 16, wherein:
R1 is methyl, ethyl, or isopropyl;
R2 is H, CH3, or gem-dimethyl;
R3 is H, CH3, OH, OCH3, —CN, or F;
R4 is selected from the group consisting of phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, and other heterocycles optionally substituted from 1 to 4 times with R14;
R5 is H or F;
R6 is H, F, or methoxy;
R7 is H;
R8is H, OH, OCH3, —CN, F, Cl, or CH3; and
X is selected from the group consisting of naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, dihydrobenzocycloheptenyl, and a fused bicyclic carbocycle or heterocycle optionally substituted from 1 to 4 times with R14.
25. The compound according to claim 24, wherein:
R4 is selected from the group consisting of furan-2-yl, 4-methyl-furan-2-yl, 5-methyl-furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, 3,5-dimethyl-isoxazol-4-yl, pyridin-2-yl, 3-methyoxy-pyridin-2-yl, 4-methoxy-pyridin-2-yl, 3-methyl-pyridin-2-yl, 4-methyl-pyridin-2-yl, 6-methyoxy-pyridin-2-yl, pyridin-3-yl, 2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, pyridin-4-yl, pyrimidin-4-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazin-2-yl, 3-methyl-pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-methyl-pyrazin-2-yl, 3-methoxy-pyrazin-2-yl, 5-methoxy-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-ethyl-pyrazin-2-yl, 6-trifluoromethyl-pyrazin-2-yl, pyridazin-3-yl, 5-methylpyridazin-3-yl, 6-methylpyridazin-3-yl, 6-dimethylamino-pyridazine-3-yl, 6-methylamino-pyridazine-3-yl, 6-amino-pyridazine-3-yl, 6-morpholin-4-yl-pyridazine-3-yl, 6-trifluoromethyl-pyridazin-3-yl, 6-cyano-pyridazine-3, pyridazin-4-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, [1,3,5]triazin-2-yl, [1,2,4]triazin-3-yl, [1,2,4]triazin-5-yl, [1,2,4]triazin-6-yl, cinnolin-3-yl, phthalazin-1-yl, phthalazin-7-yl, quinoxalin-2-yl, quinoxalin-6-yl, quinazolin-2-yl, quinazolin-4-yl, quinazolin-6-yl, quinazolin-7-yl, and 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2-yl, and 2-oxo-2H-pyridin-1-yl; and X is naphthalen-1-yl, 4-methyl-naphthalen-1-yl, naphthalen-2-yl, 1-fluoro-naphthalen-2-yl, 1-chloro-naphthalen-2-yl, 1-methoxy-naphthalen-2-yl, 1-methyl-naphthalen-2-yl, 3-fluoro-naphthalen-2-yl, 3-chloro-naphthalen-2-yl, 3-methoxy-naphthalen-2-yl, 3-cyano-naphthalen-2-yl, 4-fluoro-naphthalen-2-yl, 4-chloro-naphthalen-2-yl, 4-methyl-naphthalen-1-yl, 5-fluoro-naphthalen-2-yl, 5-chloro-naphthalen-2-yl, 5-cyano-naphthalen-2-yl, 5-methyl-naphthalen-2-yl, 6-methoxy-naphthalen-2-yl, 6-chloro-naphthalen-2-yl, 6-fluoro-naphthalen-2-yl, 6-cyano-naphthalen-2-yl, 6-methanesulfonyl-naphthalen-2-yl, 7-methoxy-naphthalen-2-yl, 7-chloro-naphthalen-2-yl, 7-fluoro-naphthalen-2-yl, 7-cyano-naphthalen-2-yl, 8-methoxy-naphthalen-2-yl, 8-chloro-naphthalen-2-yl, 8-fluoro-naphthalen-2-yl, 8-cyano-naphthalen-2-yl, 5,6,7,8-tetrahydro-naphthalen-2-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, 2-quinoxlinyl, 6-quinoxalinyl, 2-quinazolinyl, 2-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 3-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 6-phthalazinyl, 2H-chromen-3-yl or 8,9-dihydro-7H-benzocyclohepten-6-yl.
26. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 selected from the group consisting of morpholin-4-yl, 2,6-dimethyl-morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, [1,2]oxazinan-2-yl, isoxazolidin-2-yl, morpholin-4-ylmethyl, 1-methyl-1-morpholin-4-ylethyl, 1-morpholin-4-yl-cyclopropyl, piperidin-1-ylmethyl, pyrrolidin-1-ylmethyl, dimethylaminomethyl, 1-dimethylamino-1-methylethyl, 1-dimethylamino-cyclopropanyl, methylaminomethyl, 1-methyl-1-methylaminoethyl, 1-methylamino-cyclopropanyl, aminomethyl, 1-amino-1-methylethyl, 1-aminocyclopropyl, and methanesulfonyl;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl:
R8 is H, halogen —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2;
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; and
X is naphthalen-1-yl, 4-methyl-naphthalen-1-yl, naphthalen-2-yl, 1-fluoro-naphthalen-2-yl, 1-chloro-naphthalen-2-yl, 1-methoxy-naphthalen-2-yl, 1-methyl-naphthalen-2-yl, 3-fluoro-naphthalen-2-yl, 3-chloro-naphthalen-2-yl, 3-methoxy-naphthalen-2-yl, 3-cyano-naphthalen-2-yl, 4-fluoro-naphthalen-2-yl, 4-chloro-naphthalen-2-yl, 4-methyl-naphthalen-1-yl, 5-fluoro-naphthalen-2-yl, 5-chloro-naphthalen-2-yl, 5-cyano-naphthalen-2-yl, 5-methyl-naphthalen-2-yl, 6-methoxy-naphthalen-2-yl, 6-chloro-naphthalen-2-yl, 6-fluoro-naphthalen-2-yl, 6-cyano-naphthalen-2-yl, 6-methanesulfonyl-naphthalen-2-yl, 7-methoxy-naphthalen-2-yl, 7-chloro-naphthalen-2-yl, 7-fluoro-naphthalen-2-yl, 7-cyano-naphthalen-2-yl, 8-methoxy-naphthalen-2-yl, 8-fluoro-naphthalen-2-yl, 8-cyano-naphthalen-2-yl, 8-methoxy-naphthalen-2-yl, 5,6,7, 8-tetrahydro-naphthalen-2-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, 2-quinoxalinyl, 6-quinoxalinyl, 2-quinazolinyl, 2-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 3-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 6-phthalazinyl, 2H-chromen-3-yl or 8 ,9-dihydro-7H-benzocyclohepten-6-yl;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
27. The compound according to claim 16, wherein the compound is selected from the group consisting of:
2-methyl-4-(naphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(4-methylnaphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
1-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-ethyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
1,2-dimethyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2,5-dimethyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-4-ol;
4-methoxy-2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2,4-dimethyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
4-fluoro-2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
4-chloro-2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-methoxy-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
4-(7-methoxy-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
4-(8-methoxy-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
4-(8-methoxy-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
4-(8-methoxy-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
4-(8-chloro-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
4-(8-chloro-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
4-(8-chloro-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
4-(8-fluoro-naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-ol;
7-methoxy-4-(naphthalen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
2,7-dimethyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
7-fluoro-2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-methoxy-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-methyl-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(3-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(3-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(3-methoxy-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
3-(2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-naphthalene-2-carbonitrile;
4-(4-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(4-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(5-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(5-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
6-(2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-naphthalene-1-carbonitrile;
4-(5-methyl-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-methoxy-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
6-(2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-naphthalene-2-carbonitrile;
4-(6-methanesulfonyl-naphthalen-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
4-(7-methoxy-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(7-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(7-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
7-(2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-naphthalene-2-carbonitrile;
4-(8-methoxy-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(8-chloro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(8-fluoro-naphthalen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
8-(2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-naphthalene-1-carbonitrile;
2-ethyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-(6-methyl-pyridazin-3-yl)-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline;
dimethyl-[6-(2-methyl-4-naphthalene-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-amine;
methyl-[6-(2-methyl-4-naphthalene-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-amine;
6-(2-methyl-4-naphthalene-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalene-2-yl-7-(6-trifluoromethyl-pyridazin-3yl)-1,2,3,4-tetrahdyro-isoquinoline;
6-(2-methyl-4-naphthalene-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl-carbonitrile;
8-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
8-methoxy-2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
2,8-dimethyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
2-ethyl-8-fluoro-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
6-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
5-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
8-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-(3-methyl-pyrazin-2-yl)-4-(naphthalene-2-yl)-1,2,3,4-tetrahydroisoquinoline;
7-(3-methoxy-pyrazin-2yl)-2-methyl-4-(naphthalene-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-(6-methyl-pyrazin-2-yl)-4-(naphthalene-2-yl)-1,2,3,4-tetrahydroisoquinoline;
7-(6-methoxy-pyrazin-2yl)-2-methyl-4-(naphthalene-2-yl)-1,2,3,4-tetrahydroisoquinoline;
8-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
8-methoxy-2-methyl-4-(naphthalen-2-yl)-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalene-2-yl)-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
2,8-dimethyl-4-(naphthalen-2-yl)-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
8-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
8-methoxy-2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
2,8-dimethyl-4-(naphthalen-2-yl)-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
8-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
8-methoxy-2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
2,8-dimethyl-4-(naphthalen-2-yl)-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
8-fluoro-2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
8-methoxy-2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
2,8-dimethyl-4-(naphthalen-2-yl)-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalen-2-yl-7-[1,3,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalen-2-yl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalen-2-yl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalen-2-yl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
3-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
1-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
2-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
2-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
6-(2-methyl-4-naphthalen-2-yl-2-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
7-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
2-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
2-methyl-7-(morpholin-4-yl)-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-fluoro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-methoxy-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(1-methyl-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(3-fluoro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(3-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(3-methoxy-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
3-(2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinol-4-yl)-naphthalene-2-carbonitrile;
4-(4-fluoro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(4-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(5-fluoro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(5-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
6-(2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinol-4-yl)-naphthalene-1-carbonitrile;
2-methyl-4-(5-methyl-naphthalen-2-yl)-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-methoxy-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(6-fluoro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
6-(2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinol-4-yl)-naphthalene-2-carbonitrile;
4-(6-methanesulfonyl-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(7-methoxy-naphthalen-2-yl)-2-methyl-7-(motpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(7-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(7-fluoro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
7-(2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinol-4-yl)-naphthalene-2-carbonitrile;
4-(8-methoxy-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(8-chloro-naphthalen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
4-(8-fluoro-naphthalene-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
8-(2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinol-4-yl)-naphthalene-1-carbonitrile;
7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline;
2-ethyl-7-(morpholin-4-yl)-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline;
8-fluoro-2-methyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
8-methoxy-2-methyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-morpholin-4-yl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
2,8-dimethyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-ethyl-8-fluoro-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
6-fluoro-2-methyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
5-fluoro-2-methyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinolin-4-ol;
2,4-dimethyl-7-(morpholin-4-yl)-(4-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-naphthalen-2-yl-7-piperazin-1-yl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-(4-methyl-piperazin-1-yl)-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-7-(morpholin-4-yl)methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
dimethyl-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-amine;
2-methyl-[1-(4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
2-methyl-[1-(4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
methyl-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-amine;
[2-methyl-[1-(4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
[2-methyl-[1-(4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
C-(2-methyl-[1-(4-naphthalen-2-yl -1,2,3,4-tetrahydroisoquinolin-7-yl)-methyl amine;
1-(2-methyl-[1-(4-naphthalen-2-yl -1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
1-(2-methyl-[1-(4-naphthalen-2-yl -1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
1-(2-methyl-4-naphthalen-2-yl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
7-methanesulfonyl-2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
2-methyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
8-fluoro-2-methyl-4-(naphthalene-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
2,8-dimethyl-4-(naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline and
2-methyl-4-(5,6,7,8-tetrahydro-naphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline.
28. The compound according to claim 16, wherein the carbon atom designated * is in the R configuration.
29. The compound according to claim 16, wherein the carbon atom designated * is in the S configuration.
30. The compound according to claim 16, wherein the compound is a (+) stereoisomer.
31. The compound according to claim 16, wherein the compound is a (−) stereoisomer.
32. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused aromatic bicyclic carbocycle or heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14, with the proviso that X≠isoquinolinyl, naphthyl, or phthalimidyl;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl:
R8 is H, halogen —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2;
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
33. A compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14, with the provisos that (1) where X=naphthyl and R4 is NH2 or OR11, R5 cannot be H, and (2) where X=naphthyl and R5═OR11, R4 cannot be H;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R7 is gem-dimethyl;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
or an oxide thereof or a pharmaceutically acceptable salt thereof.
34. The compound according to claim 5, wherein R3 is methyl.
35. The compound according to claim 8, wherein R4 is phenyl optionally and independently substituted from 1 to 4 times with R14.
36. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 16.
37. A process for preparation of a product compound of Formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
R2 is gem-dimethyl;
R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
R7 is H;
R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
said process comprising:
treating a first intermediate compound of Formula (XVIII):
with a reducing agent, under conditions effective to produce the product compound.
Description

This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/588,448, filed Jul. 15, 2004, which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to novel 4-bicyclic carbocycle- and heterocycle-substituted tetrahydroisoquinoline derivative compounds, pharmaceutical compositions comprising such compounds, methods of using such compounds for the treatment of various neurological and psychological disorders and for combination therapy.

BACKGROUND OF THE INVENTION

It is well known that the neurotransmitters, dopamine (DA), norepinephrine (NE), and serotonin (5-HT), regulate a number of biological processes and that decreased levels of DA, NE, and 5-HT are associated with a number of neurological disorders and their physical manifestations. Significant effort has been expended on devising methods for adjusting the levels of these neurotransmitters in order to produce a desired pharmacological effect. Preventing the reuptake of these neurotransmitters in any combination of one, two, or all three of them is likely to be effective in treating these disorders. Targeting the dopamine transporter (DAT), norepinephrine transporter (NET), and the serotonin transporter (SERT) proteins has proven to be an effective way of increasing the levels of the respective monoamines.

Methylphenidate, which is currently used for the treatment of attention deficit hyperactivity disorder (ADHD), is known to be selective for inhibition of the DAT. U.S. Pat. No. 5,444,070 discloses selective inhibitors of dopamine reuptake as treatments for Parkinson's disease and drug addiction or abuse including cocaine and amphetamines.

Selective norepinephrine reuptake inhibitors (NARI) have also been disclosed. For example, U.S. Pat. No. 6,352,986 describes methods of treating ADHD, addictive disorders, and psychoactive substance use disorders with Reboxetine. In addition, Atomoxetine (Strattera®) is currently marketed as a selective NET reuptake inhibitor for ADHD.

The use of selective serotonin reuptake inhibitors (SSRI) has also been shown to be effective in treating depressive disorders. Sertraline, Citalopram, and Paroxetine are well-known examples of SSRIs used to treat disorders such as depression, obsessive compulsive disorder, and panic attacks. There are several known difficulties with the SSRI class of therapeutics, including the slow onset of action, unwanted side effects, and the existence of a significant subset of the population that is not responsive to SSRI therapy.

Selective inhibitors of DAT, NET, and SERT reuptake may also be co-administered with each other or with other drugs. U.S. Pat. No. 5,532,244 discloses the use of serotonin reuptake inhibitors in combination with a serotonin 1A antagonist for the treatment of obsessive-compulsive disorder, depression, and obesity. The use of a serotonin or norepinephrine reuptake inhibitor in combination with a neurokinin-1 receptor antagonist has been disclosed in U.S. Pat. No. 6,121,261 for the treatment of ADHD. U.S. Pat. No. 4,843,071 discloses the use of a norepinephrine reuptake inhibitor in combination with a norepinephrine precursor in the treatment of obesity, drug abuse, or narcolepsy. U.S. Pat. No. 6,596,741 discloses the use of a NE, DA, or 5-HT inhibitor with either a neurokinin-1 receptor antagonist or a serotonin-1A antagonist for the treatment of a wide variety of conditions.

Also advantageous is the use of compounds that inhibit one or more of the neurotransmitters at the same time. The antidepressant qualities of the dual NET and SERT reuptake inhibitor duloxetine is disclosed in European Patent No. 273658. Venlafaxine is disclosed in U.S. Pat. No. 4,535,186 as a reuptake inhibitor of both NE and 5-HT for the treatment of depressive disorders. U.S. Pat. No. 6,635,675 discloses the use of the dual NE and 5-HT reuptake inhibitor milnacipran for the treatment of chronic fatigue syndrome and fibromyalgia syndrome. In addition, dual NE and 5-HT reuptake inhibitors are disclosed in U.S. Pat. No. 6,136,083 for the treatment of depression. It is also recognized that compounds which inhibit the reuptake of NE, DA, and 5-HT in varying ratios not specifically mentioned here would also be advantageous.

Treating illnesses by inhibiting the reuptake of all three of the monoamines, either through combination therapy or “triple inhibitors,” may have clinical benefit as well. PCT International Publication Nos. WO 03/101453 and WO 97/30997 disclose a class of compounds which are active against all three monoamine transporters. The rationale for the inclusion of a dopamine-enhancing component in antidepressant therapy includes observed deficits in dopaminergic function, the success of combination therapy with dopamine agonists and traditional antidepressants, and an increased sensitivity in dopamine receptors due to chronic antidepressant administration (Skolnick et al., Life Sciences 73:3175-3179 (2003)). As such, inhibitory activity against DA reuptake, in addition to NE and 5-HT reuptake, is expected to provide a more rapid onset of antidepressant effect, compared to other mixed inhibitors which are selective for NET and SERT over DAT. In addition, PCT International Publication No. WO 03/049736 discloses a series of 4-substituted piperidines, each of which displays similar activity against DA, NE and 5-HT transporters. Bicyclo[2.2.1]heptanes (Axford et al., Bioorg Med Chem Lett 13:3277-3280 (2003)) and azabicyclo[3.1.0]hexanes (Skolnick et al., Eur J Pharm, 461:99-104 (2003)) are also described as triple inhibitors of the three monoamine transporters.

U.S. Pat. No. 3,947,456 discloses tetrahydroisoquinolines which are said to have utility as antidepressants. U.S. Pat. No. 3,666,763 describes the use of phenyl tetrahydroisoquinoline derivatives as antidepressants and antihypotensives. Canadian Patent Application No. 2,015,114 discloses the use of phenyl tetrahydroisoquinoline derivatives as antidepressants; the compounds described therein are apparently nonselective as to norepinephrine, serotonin, and dopamine uptake. United Kingdom Patent Application No. 2,271,566 discloses the use of phenyl tetrahydroisoquinoline derivatives as anti-HIV agents. PCT International Publication No. WO 98/40358 discloses the use of phenyl tetrahydroisoquinoline derivatives to be useful in the treatment of disorders of glucose metabolic pathways. PCT International Publication No. WO 97/36876 discloses the use of phenyl tetrahydroisoquinoline derivatives as anticancer agents. PCT International Publication No. WO 97/23458 also describes 4-phenyl-substituted tetrahydroisoquinolines as NMDA receptor ligands useful for conditions associated with neuronal loss. Phenyl-substituted tetrahydroisoquinolines are also described in Mondeshka et al., II Farmaco 49:475-481 (1994).

U.S. Pat. No. 6,579,885 discloses the use of 7-aryl-substituted tetrahydroisoquinolines as being useful for the treatment of disorders involving decreased availability of serotonin, norepinephrine, or dopamine. Tupper et al., J Heterocyclic Chem 33:1123-1129 (1996) describes the synthesis of tetrahydroisoquinolines substituted with a 2- or 3-thienyl group in the 4 position as possible dopamine D1 and D2 antagonists. Prat et al., J Heterocyclic Chem 37:767-771 (2000) describes the synthesis of N-methyl-4-pyridyl-1,2,3,4-tetrahydroisoquinolines, as well as the 2-pyridyl and 3-pyridyl analogs, which were designed as potential serotonin analogs, but no activity was reported. Chandrasekhar et al., Tetrahedron Lett 43:1885-1888 (2002) described the synthesis of trans-4-benzo[1,3]dioxol-5-yl-2-benzyl-3-methyl-1,2,3,4-tetrahydroisoquinoline; however, neither usage nor activity was reported. Lopez et al., Tetrahedron 50:9097-9106 (1994) described the synthesis of 2-(1,2,3,4-tetrahydroisoquinolin-4-yl)-quinolin-3-ol; however, neither usage nor activity was reported. Uno et al., J Heterocyclic Chem 38:341-346 (1991) described the synthesis of 1-ethyl-1′-pentafluoroethyl-1,2,3,4-tetrahydro-[4,4′]bis(isoquinoline); however, neither usage nor activity was reported.

Nomifensine®, which is a 4-phenyl-substituted tetrahydroisoquinoline derivative, is known to inhibit the neuronal uptake of dopamine and other catecholamines and has shown clinical efficacy for ADHD. However, long term administration of Nomifensine® resulted in fatal immune hemolytic anemia in a very small number of patients causing the manufacturer to discontinue this drug from the market. Thus, there continues to remain a need to develop novel compounds which treat ADHD but do not have the serious side effects associated with Nomifensine® or the currently prescribed psychostimulants.

The present invention is directed to achieving these objectives.

SUMMARY OF THE INVENTION

The compounds of the present invention are represented by the chemical structure found in Formula (I):


wherein:

  • the carbon atom designated * is in the R or S configuration;
  • X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —R9, and —NR9R10; or R2 is gem-dimethyl;
  • R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R7 is gem-dimethyl;
  • R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
  • R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
  • R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
  • R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
  • R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
  • R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
  • R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
  • n is 0, 1, or 2; and
  • R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • or an oxide thereof or a pharmaceutically acceptable salt thereof.

The compounds of the present invention are also represented by the chemical structure found in Formula (I):


wherein:

  • the carbon atom designated * is in the R or S configuration;
  • X is a fused aromatic bicyclic carbocycle or heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14, with the proviso that X≠isoquinolinyl, naphthyl, or phthalimidyl;
  • R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or R2 is gem-dimethyl;
  • R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-CC 3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R7 is gem-dimethyl;
  • R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
  • R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
  • R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
  • R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
  • R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
  • R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
  • R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
  • n is 0, 1, or 2; and
  • R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • or an oxide thereof or a pharmaceutically acceptable salt thereof.

In addition, the compounds of the present invention are represented by the chemical structure found in Formula (I):


wherein:

  • the carbon atom designated * is in the R or S configuration;
  • X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14, with the provisos that (1) where X=naphthyl and R4 is NH2 or OR11, R5 cannot be H, and (2) where X=naphthyl and R5═OR11, R4 cannot be H;
  • R1is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
  • R2 is gem-dimethyl;
  • R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R7 is gem-dimethyl;
  • R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
  • R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
  • R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
  • R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;

R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or

  • R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
  • R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
  • n is 0, 1, or 2; and
  • R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • or an oxide thereof or a pharmaceutically acceptable salt thereof.

Another aspect of the present invention relates to a process for preparation of a product compound of Formula (I):


wherein:

  • the carbon atom designated * is in the R or S configuration;
  • X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
  • R2 is gem-dimethyl;
  • R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R7 is H;
  • R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
  • R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
  • R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
  • R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
  • R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
  • R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
  • R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
  • n is 0, 1, or 2; and
  • R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10. The process involves treating a first intermediate compound of Formula (XVIII):


with a reducing agent, under conditions effective to produce the product compound.

Results of recent clinical investigations with drugs, such as duloxetine, venlafaxine, atomoxetine, and others that work mechanistically through transporter reuptake inhibition, provide evidence that the potency and selectivity are important factors in leading to drugs with an improved efficacy, improved therapeutic index, and utility for treatment of new clinical indications. Duloxetine, a dual action transporter reuptake inhibitor, is a selective inhibitor for serotonin transporter protein (“SERT”) and norepinephrine transporter protein (“NET”) reuptake (Sorbera et al., Drugs of the Future, 25(9):907-916 (2000), which is hereby incorporated by reference in its entirety) and is in clinical development for the treatment of depression and stress urinary incontinence. In clinical studies, researchers attribute the effect of the medication on a broad spectrum of depression symptoms, which include emotional and painful physical symptoms as well as anxiety, to its dual reuptake inhibition of both serotonin and norepinephrine. Venlafaxine, which is also reported to be a selective serotonin and norepinephrine reuptake inhibitor (SNRI class), has been reported to exhibit a more rapid onset of action. This has been a drawback with the first generation antidepressants, i.e., the single action serotonin selective reuptake inhibitors (SSRI class). Prozac®, the prototype drug in this class, can take four weeks or longer for full anti-depressive activity to take effect.

Atomoxetine (Strattera®) was recently approved for the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine is a norepinephrine selective transporter reuptake inhibitor. Unlike Ritalin®, one of the most frequently used drugs for treatment of ADHD, atomoxetine has little or no activity at the dopamine transporter. As a result, atomoxetine has the advantage that it is not scheduled as a controlled substance because it has minimal potential for substance abuse.

In a manner similar to the newer clinical agents like atomoxetine, duloxetine and venlafaxine, the compounds of the present invention may exhibit improved efficacy towards broader symptoms of depression. The compounds of the present invention may also exhibit more rapid onset of action in the treatment of CNS diseases like depression. In addition to providing improved efficacy, the compounds of the present invention may also exhibit fewer undesirable side effects. Finally, because the compounds of the present invention possess a diverse transporter reuptake inhibition profile, they are expected to be useful for a wider variety of CNS disorders.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the present invention are represented by the chemical structure found in Formula (I):


wherein:

  • the carbon atom designated * is in the R or S configuration;
  • X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R1 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • R2 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or C1-C6 haloalkyl, each of which is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10; or
  • R2 is gem-dimethyl;
  • R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —R9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R5 and R6 are each independently selected from the group consisting of: H, halogen, —OR11, —S(O)RnR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, and phenyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9;
  • R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl which is optionally substituted 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R7 is gem-dimethyl;
  • R8 is H, halogen, —OR9, —SR9, C1-C6 alkyl, —CN, or —NR9R10;
  • R9 and R10 are each independently selected from the group consisting of: H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, and benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy; or
  • R9 and R10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, thiomorpholine, [1,2]oxazinane, isoxazolidine, or 2-oxo-2H-pyridine, which is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
  • R11 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R13, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
  • R12 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; or
  • R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R9 and R10 or R11 and R12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
  • R13 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
  • n is 0, 1, or 2; and
  • R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11C(O)NR12R13, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —OR9, and —NR9R10;
  • or an oxide thereof or a pharmaceutically acceptable salt thereof.

As used above, and throughout the description of the invention, the following terms, unless otherwise indicated, shall be understood to have the following meanings.

The term “fused bicyclic carbocycle” means a bicyclic ring system consisting of about 8 to 11 ring carbon atoms, preferably 9 or 10. One or both of the rings is/are aromatic. Representative fused bicyclic carbocycles include indenyl, indanyl, naphthyl (or naphthalenyl), dihydronaphthyl, tetrahydronapthyl, benzocycloheptenyl, dihydrobenzocycloheptenyl, tetrahydrobenzocyloheptenyl, and the like.

The term “fused bicyclic heterocycle” means a bicyclic ring system consisting of about 8 to 11 ring atoms, preferably 9 or 10, in which one or more of the atoms in the ring system is/are element(s) other than carbon, for example, nitrogen, oxygen, or sulfur. The prefix aza, oxa, or thia before heterocycle means that at least a nitrogen, oxygen, or sulfur atom, respectively, is present as a ring atom. A nitrogen atom of a heteroaryl is optionally oxidized to the corresponding N-oxide. Representative fused bicyclic heterocycles include benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, chromenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, and the like.

The term “alkyl” means an aliphatic hydrocarbon group which may be straight or branched having about 1 to about 6 carbon atoms in the chain. “Branched” means that one or more lower alkyl groups, such as methyl, ethyl, or propyl, are attached to a linear alkyl chain. Exemplary alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, n-pentyl, and 3-pentyl.

The term “alkenyl” means an aliphatic hydrocarbon group containing a carbon-carbon double bond and which may be straight or branched having about 2 to about 6 carbon atoms in the chain. Preferred alkenyl groups have 2 to about 4 carbon atoms in the chain. “Branched” means that one or more lower alkyl groups, such as methyl, ethyl, or propyl, are attached to a linear alkenyl chain. Exemplary alkenyl groups include ethenyl, propenyl, n-butenyl, and i-butenyl.

The term “alkynyl” means an aliphatic hydrocarbon group containing a carbon-carbon triple bond and which may be straight or branched having about 2 to about 6 carbon atoms in the chain. Preferred alkynyl groups have 2 to about 4 carbon atoms in the chain. “Branched” means that one or more lower alkyl groups, such as methyl, ethyl, or propyl, are attached to a linear alkynyl chain. Exemplary alkynyl groups include ethynyl, propynyl, n-butynyl, 2-butynyl, 3-methylbutynyl, and n-pentynyl.

The term “aryl” means an aromatic monocyclic or multicyclic ring system of 6 to about 14 carbon atoms, preferably of 6 to about 10 carbon atoms. Representative aryl groups include phenyl and naphthyl. The terms “naphthyl” and “naphthalenyl” are used interchangeably.

The term “alkoxy” means an alkyl-O-group wherein the alkyl group is as herein described. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, and heptoxy.

The term “compounds of the invention”, and equivalent expressions are meant to embrace compounds of general Formula (I) as hereinbefore described, which expression includes the prodrugs, the pharmaceutically acceptable salts, and the solvates, e.g., hydrates, where the context so permits. Similarly, reference to intermediates, whether or not they themselves are claimed, is meant to embrace their salts and solvates, where the context so permits. For the sake of clarity, particular instances, when the context so permits, are sometimes indicated in the text, but these instances are purely illustrative and it is not intended to exclude other instances when the context so permits.

The term “cycloalkyl” means a non-aromatic monocyclic or multicyclic ring system of about 3 to about 7 carbon atoms, preferably of about 5 to about 7 carbon atoms. Exemplary monocyclic cycloalkyl groups include cyclopentyl, cyclohexyl, cycloheptyl, and the like.

The term “cycloalkylalkyl” means a cycloalkyl-alkyl-group in which the cycloalkyl and alkyl are as defined herein. Exemplary cycloalkylalkyl groups include cyclopropylmethyl and cyclopentylmethyl.

The term “halo” or “halogen” means fluoro, chloro, bromo, or iodo.

The term “haloalkyl” means both branched and straight-chain alkyl substituted with one or more halogen, wherein the alkyl group is as herein described.

The term “haloalkoxy” means a C1-4 alkoxy group substituted by at least one halogen atom, wherein the alkoxy group is as herein described.

The term “substituted” or “substitution” of an atom means that one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded. “Unsubstituted” atoms bear all of the hydrogen atoms dictated by their valency. When a substituent is keto (i.e., =O), then 2 hydrogens on the atom are replaced. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds; by “stable compound” or “stable structure” is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

The term “pharmaceutically acceptable salts” means the relatively non-toxic, inorganic and organic acid addition salts, and base addition salts of compounds of the present invention. These salts can be prepared in situ during the final isolation and purification of the compounds. In particular, acid addition salts can be prepared by separately reacting the purified compound in its free base form with a suitable organic or inorganic acid and isolating the salt thus formed. Exemplary acid addition salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactiobionate, sulphamates, malonates, salicylates, propionates, methylene-bis-b-hydroxynaphthoates, gentisates, isothionates, di-p-toluoyltartrates, methanesulphonates, ethanesulphonates, benzenesulphonates, p-toluenesulphonates, cyclohexylsulphamates and quinateslaurylsulphonate salts, and the like. (See, for example Berge et al., “Pharmaceutical Salts,” J Pharm Sci, 66:1-sup. 19 (1977) and Remington's Pharmaceutical Sciences, 17th ed, Easton, Pa., Mack Publishing Company, p. 1418 (1985), which are hereby incorporated by reference in their entirety.) Base addition salts can also be prepared by separately reacting the purified compound in its acid form with a suitable organic or inorganic base and isolating the salt thus formed. Base addition salts include pharmaceutically acceptable metal and amine salts. Suitable metal salts include the sodium, potassium, calcium, barium, zinc, magnesium, and aluminum salts. The sodium and potassium salts are preferred. Suitable inorganic base addition salts are prepared from metal bases which include sodium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, and zinc hydroxide. Suitable amine base addition salts are prepared from amines which have sufficient basicity to form a stable salt and preferably include those amines which are frequently used in medicinal chemistry because of their low toxicity and acceptability for medical use. Examples of such amines include ammonia, ethylenediamine, N-methyl-glucamine, lysine, arginine, ornithine, choline, N,N′-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, diethylamine, piperazine, tris(hydroxymethyl)-aminomethane, tetramethylammonium hydroxide, triethylamine, dibenzylamine, ephenamine, dehydroabietylamine, N-ethylpiperidine, benzylamine, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, ethylamine, basic amino acids such as lysine and arginine, dicyclohexylamine, and the like.

The term “pharmaceutically acceptable prodrugs” as used herein means those prodrugs of the compounds useful according to the present invention which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals with undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term “prodrug” means compounds that are rapidly transformed in vivo to yield the parent compound of the above formula, for example by hydrolysis in blood. Functional groups which may be rapidly transformed, by metabolic cleavage in vivo, form a class of groups reactive with the carboxyl group of the compounds of the present invention. They include, but are not limited to, such groups as alkanoyl (such as acetyl, propionyl, butyryl, and the like), unsubstituted and substituted aroyl (such as benzoyl and substituted benzoyl), alkoxycarbonyl (such as ethoxycarbonyl), trialkylsilyl (such as trimethyl- and triethysilyl), monoesters formed with dicarboxylic acids (such as succinyl), and the like. Because of the ease with which the metabolically cleavable groups of the compounds useful according to this invention are cleaved in vivo, the compounds bearing such groups act as pro-drugs. The compounds bearing the metabolically cleavable groups have the advantage that they may exhibit improved bioavailability as a result of enhanced solubility and/or rate of absorption conferred upon the parent compound by virtue of the presence of the metabolically cleavable group. A thorough discussion of prodrugs is provided in the following: Bundgaard, ed., Design of Prodrugs, Elsevier (1985); Widder et al., Methods in Enzymology, ed., Academic Press, 42:309-396 (1985); “Design and Applications of Prodrugs,” Krogsgaard-Larsen, ed., A Textbook of Drug Design and Development, Chapter 5:113-191 (1991); Bundgaard, “Advanced Drug Delivery Reviews,” 8:1-38 (1992); Bundgaard et al., Journal of Pharmaceutical Sciences, 77:285 (1988); Nakeya et al., Chem Pharm Bull, 32:692 (1984); Higuchi, “Pro-drugs as Novel Delivery Systems” Roche, ed., A.C.S. Symposium Series, Vol. 14, and “Bioreversible Carriers in Drug Design” American Pharmaceutical Association and Pergamon Press (1987), which are hereby incorporated by reference in their entirety. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohol and amine functional groups in the compounds of the invention.

The term “therapeutically effective amounts” is meant to describe an amount of compound of the present invention effective in increasing the levels of serotonin, norepinephrine, or dopamine at the synapse and, thus, producing the desired therapeutic effect. Such amounts generally vary according to a number of factors well within the purview of ordinarily skilled artisans given the description provided herein to determine and account for. These include, without limitation: the particular subject, as well as its age, weight, height, general physical condition and medical history, the particular compound used, as well as the carrier in which it is formulated and the route of administration selected for it, and the nature and severity of the condition being treated.

The term “pharmaceutical composition” means a composition comprising a compound of Formula (I) and at least one component selected from pharmaceutically acceptable carriers, diluents, adjuvants, excipients, or vehicles, such as preserving agents, fillers, disintegrating agents, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavoring agents, perfuming agents, antibacterial agents, antifungal agents, lubricating agents and dispensing agents, depending on the nature of the mode of administration and dosage forms. Examples of suspending agents include ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example, sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monosterate and gelatin. Examples of suitable carriers, diluents, solvents or vehicles include water, ethanol, polyols, suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters, such as ethyl oleate. Examples of excipients include lactose, milk sugar, sodium citrate, calcium carbonate, dicalcium phosphate phosphate. Examples of disintegrating agents include starch, alginic acids, and certain complex silicates. Examples of lubricants include magnesium stearate, sodium lauryl sulphate, talc, as well as high molecular weight polyethylene glycols.

The term “pharmaceutically acceptable” means it is, within the scope of sound medical judgment, suitable for use in contact with the cells of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio.

The term “pharmaceutically acceptable dosage forms” means dosage forms of the compound of the invention, and includes, for example, tablets, dragees, powders, elixirs, syrups, liquid preparations, including suspensions, sprays, inhalants tablets, lozenges, emulsions, solutions, granules, capsules and suppositories, as well as liquid preparations for injections, including liposome preparations. Techniques and formulations generally may be found in Remington's Pharmaceutical Sciences, 17th ed, Easton, Pa., Mack Publishing Company (1985), which is hereby incorporated by reference in its entirety.

One embodiment of the present invention relates to the compound of the Formula (I) where:

  • X is selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R1 is H or C1-C6 alkyl;
  • R2 is H, C1-C6 alkyl, or C1-C6 haloalkyl;
  • R3 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted from 1 to 3 times with a substituent selected from the group consisting of: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy, —CN, and —OR9;
  • R4 is H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, —C(O)NR11R12, —NR9R10, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of: C1-C3 alkyl, halogen, —CN, —OR9, —NR9R10, and phenyl, which is optionally substituted from 1 to 3 times with a substituent selected from the group consisting of: halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, and —OR9; or
  • R4 is phenyl, naphthyl, indenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, [1,2,4]triazinyl, [1,3,5]triazinyl, triazolyl, furanyl, thiophenyl, pyranyl, indazolyl, benzimidazolyl, quinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, benzthiazolyl, purinyl, isothiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, or other heterocycles optionally substituted with substituents (1 to 4 in number) as defined below in R14;
  • R5 and R6 are each independently selected from H, halogen, C1-C6 alkyl, or C1-C4 alkoxyalkyl;
  • R7 is H or C1-C6 alkyl;
  • R8 is H, halogen, —OR9, —SR9, —CN, C1-C6 alkyl, —CN, or —NR9R10;
  • R14 is independently selected at each occurrence from a substituent selected from the group consisting of: halogen, —NO2, —OR11, —NR11R12, —NR11C(O)R12, —NR11C(O)2R12, —NR11 C(O)NR12R13, —S(O)n R12, —CN, —C(O)R12, —C(O)NR11R12, C1-CC 6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl, where C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and C4-C7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of: C1-C3 alkyl, halogen, aryl, —CN, —R9, and —NR9R10.

Another embodiment of the present invention relates to the compound of Formula (I) where:

  • X is benzofuran-2-yl, 5-chloro-benzofuran-2-yl, 4-fluoro-benzofuran-2-yl, 5-fluoro-benzofuran-2-yl, 5-methoxy-benzofuran-2-yl, 6-fluoro-benzofuran-2-yl, 7-fluoro-benzofuran-2-yl, 7-methoxy-benzofuran-2-yl benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, benzofuran-7-yl, 2,3-dihydro-benzofuran-5-yl, benzo[b]thiophen-2-yl, 4-chloro-benzo[b]thiophen-2-yl, 4-fluoro-benzo[b]thiophen-2-yl, 4-methoxy-benzo[b]thiophen-2-yl, 5-chloro-benzo[b]thiophen-2-yl, 5-fluoro-benzo[b]thiophen-2-yl, 6-chloro-benzo[b]thiophen-2-yl, 6-fluoro-benzo[b]thiophen-2-yl, 7-chloro-benzo[b]thiophen-2-yl, 7-fluoro-benzo[b]thiophen-2-yl, 1,1-dioxo-1H-1λ6-benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, 2-methylbenzo[b]thiophen-5-yl, 2-chloro-benzo[b]thiophen-5-yl, 3-trifluoromethyl-benzo[b]thiophen-5-yl, 4-cyano-benzo[b]thiophen-5-yl, 4-methoxy-benzo[b]thiophen-5-yl, 4-hydroxy-benzo[b]thiophen-5-yl, 4-methyl-benzo[b]thiophen-5-yl, 1,1-dioxo-1H-1λ6-benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, 2-chloro-benzo[b]thiophen-6-yl, 3-trifluoromethyl-benzo[b]thiophen-6-yl, 7-methoxy-benzo[b]thiophen-6-yl, 7-hydroxy-benzo[b]thiophen-6-yl, 7-methyl-benzo[b]thiophen-6-yl, 1,1-dioxo-1H-1λ6-benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, 1H-indazol-1-yl, 1H-indazol-3-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1-methyl-indazol-5-yl, 6-methoxy-1H-indazol-5-yl, 7-methoxy-1H-indazol-5-yl, 7-fluoro-1H-indazol-5-yl, 7-chloro-1H-indazol-5-yl, 7-methoxy-1H-indazol-5-yl, 1H-indazol-6-yl, 1-methyl-indazol-6-yl, 7-fluoro-1H-indazol-6-yl, 1H-indazol-7-yl, indol-1-yl, 1-methyl-indol-2-yl, 1H-indol-2-yl, 7-fluoro-1H-indol-2-yl, 1H-indol-3-yl, 1H-indol-4-yl, 1H-indol-5-yl, 1-methyl-indol-5-yl, 7-fluoro-1H-indol-5-yl, 1H-indol-6-yl, 1-methyl-indol-6-yl, 7-fluoro-1H-indol-6-yl, 2H-isoindol-1-yl, 2H-isoindol-2-yl, 2H-isoindol-4-yl, 2H-isoindol-5-yl, indolizin-1-yl, indolizin-2-yl, indolizin-3-yl, indolizin-5-yl, indolizin-6-yl, indolizin-7-yl, indolizin-8-yl, benzooxazol-2-yl, benzooxazol-4-yl, benzooxazol-5-yl, 2-methyl-benzooxazol-5-yl, benzooxazol-6-yl, 2-methyl-benzooxazol-6-yl, benzooxazol-7-yl, benzothiazol-2-yl, benzothiazol-4-yl, benzothiazol-5-yl, 2-methylbenzothiazol-5-yl, benzothiazol-6-yl, 2-methylbenzothiazol-6-yl, benzothiazol-7-yl, benzoisothiazol-4-yl, benzoisothiazol-5-yl, benzoisothiazol-6-yl, benzoisothiazol-7-yl, benzoisoxazolyl-4-yl, benzoisoxazolyl-5-yl, benzoisoxazolyl-6-yl, benzoisoxazolyl-7-yl, imidazo[1,2-a]pyridine-2-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridine-7-yl, pyrazolo[1,5-a]pyridine-2-yl, pyrazolo[1,5-a]pyridin-5-yl, pyrazolo[1,5-a]pyridin-6-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, thieno[2,3-b]pyridin-2-yl, [1,2,4]triazolo[4,3-a]pyridin-7-yl, thieno[2,3-b]pyridin-6-yl, thieno[2,3-b]pyridin-5-yl, thieno[3,2-b]pyridin-2-yl, thieno[3,2-b]pyridin-5-yl, thieno[3,2-b]pyridin-6-yl, 1H-pyrrolo[2,3-b]pyridin-2-yl, 1H-pyrrolo[2,3-b]pyridin-5-yl, 1H-pyrrolo[2,3-b]pyridin-6-yl, 3H-inden-5-yl, indan-5-yl, naphthalen-1-yl, 4-methyl-naphthalen-1-yl, naphthalen-2-yl, 1-fluoro-naphthalen-2-yl, 1-chloro-naphthalen-2-yl, 1-methoxy-naphthalen-2-yl, 1-methyl-naphthalen-2-yl, 3-fluoro-naphthalen-2-yl, 3-chloro-naphthalen-2-yl, 3-methoxy-naphthalen-2-yl, 3-cyano-naphthalen-2-yl, 4-fluoro-naphthalen-2-yl, 4-chloro-naphthalen-2-yl, 4-methyl-naphthalen-1-yl, 5-fluoro-naphthalen-2-yl, 5-chloro-naphthalen-2-yl, 5-cyano-naphthalen-2-yl, 5-methyl-naphthalen-2-yl, 6-methoxy-naphthalen-2-yl, 6-chloro-naphthalen-2-yl, 6-fluoro-naphthalen-2-yl, 6-cyano-naphthalen-2-yl, 6-methanesulfonyl-naphthalen-2-yl, 7-methoxy-naphthalen-2-yl, 7-chloro-naphthalen-2-yl, 7-fluoro-naphthalen-2-yl, 7-cyano-naphthalen-2-yl, 8-methoxy-naphthalen-2-yl, 8-chloro-naphthalen-2-yl, 8-fluoro-naphthalen-2-yl, 8-cyano-naphthalen-2-yl, 5,6,7,8-tetrahydro-naphthalen-2-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, 2-quinoxalinyl, 6-quinoxalinyl, 2-quinazolinyl, 2-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 3-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 6-phthalazinyl, 2H-chromen-3-yl, or 8,9-dihydro-7H-benzocyclohepten-6-yl;
  • R1 is H, methyl, ethyl, or isopropyl;
  • R2 is H, methyl, or gem-dimethyl;
  • R3 is H, methyl, hydroxy, methoxy, fluoro, chloro, or CN;
  • R4 is H, C1-C6 alkyl, fluoro, chloro, —OR11, morpholin-4-yl, 2,6-dimethyl-morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, piperidin-1-yl, pyrrolidin-1-yl, morpholin-4-ylmethyl, 1-methyl-1-morpholin-4-ylethyl, 1-morpholin-4-yl-cyclopropyl, piperidin-1-ylmethyl, pyrrolidin-1-ylmethyl, dimethylaminomethyl, 1-dimethylamino-1-methylethyl, 1-dimethylamino-cyclopropanyl, methylaminomethyl, 1-methyl-1-methylaminoethyl, 1-methylamino-cyclopropyl, aminomethyl, 1-amino-1-methylethyl, 1-aminocyclopropyl, methanesulfonyl or —CN; or
  • R4 is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 3,5-difluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-dimethylaminophenyl, 2-methylsufonylphenyl, 3-methylsufonylphenyl, 4-methylsufonylphenyl, 2-trifuoromethylphenyl, 3-trifuoromethylphenyl, 4-trifuoromethylphenyl, furan-2-yl, 4-methyl-furan-2-yl, 5-methyl-furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, 3,5-dimethyl-isoxazol-4-yl, pyridin-2-yl, 3-methyoxy-pyridin-2-yl, 4-methoxy-pyridin-2-yl, 3-methyl-pyridin-2-yl, 4-methyl-pyridin-2-yl, 6-methyoxy-pyridin-2-yl, pyridin-3-yl, 2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, pyridin-4-yl, pyrimidin-4-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyrazin-2-yl, 3-methyl-pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-methyl-pyrazin-2-yl, 3-methoxy-pyrazin-2-yl, 5-methoxy-pyrazin-2-yl, 6-methoxy-pyrazin-2-yl, 6-ethyl-pyrazin-2-yl, 6-trifluoromethyl-pyrazin-2-yl, pyridazin-3-yl, 5-methylpyridazin-3-yl, 6-methylpyridazin-3-yl, 6-dimethylamino-pyridazin-3-yl, 6-methylamino-pyridazin-3-yl, 6-amino-pyridazin-3-yl, 6-morpholin-4-yl-pyridazin-3-yl, 6-trifluoromethyl-pyridazin-3-yl, 6-cyano-pyridazin-3-yl, pyridazin-4-yl, 2-quinolinyl, 3-quinolinyl, 6-quinolinyl, 7-quinolinyl, 1-isoquinolinyl, 3-isoquinolinyl, 6-isoquinolinyl, 7-isoquinolinyl, [1,3,5]triazin-2-yl, [1,2,4]triazin-3-yl, [1,2,4]triazin-5-yl, [1,2,4]triazin-6-yl, cinnolin-3-yl, phthalazin-1-yl, phthalazin-7yl, quinoxalin-2-yl, quinoxalin-6-yl, quinazolin-2-yl, quinazolin-4-yl, quinazolin-6-yl, quinazolin-7-yl, 3-oxo-[1,2,4]triazolo[4,3-a]pyridin-2-yl, or 2-oxo-2H-pyridin-1-yl;
  • R5 is H, fluoro, chloro, methyl, —OH, or methoxy;
  • R6 is H; fluoro, chloro, methyl, —OH, or methoxy;
  • R7is H; and
  • R8 is H, fluoro, chloro, —OH, —CN, methyl, or ethyl.

Another embodiment of the present invention relates to the compound of Formula (I) where the carbon atom designated * is in the R configuration.

Another embodiment of the present invention relates to the compound of Formula (I) where the carbon atom designated * is in the S configuration.

Another embodiment of the present invention relates to a mixture of stereoisomeric compounds of Formula (I) where the carbon atom designated * is in the S or R configuration.

Within these embodiments, the selection of a particular preferred substituent at any one of R1-R8 does not affect the selection of a substituent at any of the others of R1-R8. That is, the specific compounds provided herein have any of the specific substituents at any of the positions. For example, as described hereinabove, R1 is preferably C1-C6 alkyl; the selection of R1 as any one of C1, C2, C3, C4, C5 or C6 alkyl, does not limit the choice of R2 in particular to any one of H, C1-C6 alkyl, or C1-C6 haloalkyl. Rather, for R1 as any of C1, C2, C3, C4, C5 or C6 alkyl, R2 is any of H, C1, C2, C3, C4, C5 or C6 alkyl or C1, C2, C3, C4, C5 or C6 haloalkyl. Similarly, selection of R2 as any of H, C1, C2, C3, C4, C5 or C6 alkyl or C1, C2, C3, C4, C5 or C6 haloalkyl does not limit the selection of R3 in particular to any one of H, halogen, —OR11, —S(O)nR12, —CN, —C(O)R12, C1-C6 alkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, or substituted C4-C7 cycloalkylalkyl.

Other specific compounds of the invention are those with the following substituents:

TABLE A
X R1 R2 R3 R4 R5 R6 R7 R8
benzo[b]thiophen-2-yl H H H H H H H H
benzo[b]thiophen-2-yl H Me H H H H H H
benzo[b]thiophen-2-yl Me H H H H H H H
benzo[b]thiophen-2-yl Et H H H H H H H
benzo[b]thiophen-2-yl Me Me H H H H H H
4-fluoro- Me H H H H H H H
benzo[b]thiophen-2-yl
5-fluoro-benzo[b]thiophen- Me H H H H H H H
2-yl
6-fluoro-benzo[b]thiophen- Me H H H H H H H
2-yl
7-fluoro-benzo[b]thiophen- Me H H H H H H H
2-yl
4-chloro- Me H H H H H H H
benzo[b]thiophen-2-yl
5-chloro- Me H H H H H H H
benzo[b]thiophen-2-yl
6-chloro- Me H H H H H H H
benzo[b]thiophen-2-yl
7-chloro- Me H H H H H H H
benzo[b]thiophen-2-yl
4-methoxy- Me H H H H H H H
benzo[b]thiophen-2-yl
5-methoxy- Me H H H H H H H
benzo[b]thiophen-2-yl
6-methoxy- Me H H H H H H H
benzo[b]thiophen-2-yl
7-methoxy- Me H H H H H H H
benzo[b]thiophen-2-yl
1,1-dioxo-1H-1λ6- Me H H H H H H H
benzo[b]thiophen-2-yl
benzo[b]thiophen-2-yl Me H H H H H H OH
benzo[b]thiophen-2-yl Me H H H H H H OMe
benzo[b]thiophen-2-yl Me H H H H H H Me
benzo[b]thiophen-2-yl Me H H H H H H CN
benzo[b]thiophen-2-yl Me H H H H H H F
benzo[b]thiophen-2-yl Me H H H H H H Cl
benzo[b]thiophen-2-yl Me H H H H Me H H
benzo[b]thiophen-2-yl Me H H OH H H H H
benzo[b]thiophen-2-yl Me H H OMe H H H H
benzo[b]thiophen-2-yl Me H H Me H H H H
benzo[b]thiophen-2-yl Me H H F H H H H
benzo[b]thiophen-2-yl Me H H pyridazin-3-yl H H H H
4-fluoro-benzo[b]thiophen- Me H H pyridazin-3-yl H H H H
2-yl
5-fluoro-benzo[b]thiophen- Me H H pyridazin-3-yl H H H H
2-yl
6-fluoro-benzo[b]thiophen- Me H H pyridazin-3-yl H H H H
2-yl
7-fluoro-benzo[b]thiophen- Me H H pyridazin-3-yl H H H H
2-yl
benzo[b]thiophen-2-yl Et H H pyridazin-3-yl H H H H
benzo[b]thiophen-2-yl Me H H 6-methylpyridazin- H H H H
3-yl
benzo[b]thiophen-2-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
benzo[b]thiophen-2-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
benzo[b]thiophen-2-yl Me H H 6-amino-pyridazin- H H H H
3-yl
benzo[b]thiophen-2-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
benzo[b]thiophen-2-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
benzo[b]thiophen-2-yl Me H H 6-cyano-pyridazin- H H H H
3-yl
benzo[b]thiophen-2-yl Me H F pyridazin-3-yl H H H H
benzo[b]thiophen-2-yl Me H OMe pyridazin-3-yl H H H H
benzo[b]thiophen-2-yl Me H OH pyridazin-3-yl H H H H
benzo[b]thiophen-2-yl Me H Me pyridazin-3-yI H H H H
benzo[b]thiophen-2-yl Et H F pyridazin-3-yl H H H H
benzo[b]thiophen-2-yl Me H H pyridazin-3-yl F H H H
benzo[b]thiophen-2-yl Me H H pyridazin-3-yl H F H H
benzo[b]thiophen-2-yl Me H H pyridazin-3-yl H H H OH
benzo[b]thiophen-2-yl Me H H pyridazin-3-yl H H H Me
benzo[b]thiophen-2-yl Me H H pyridazin-4-yl H H H H
benzo[b]thiophen-2-yl Me H F pyridazin-4-yl H H H H
benzo[b]thiophen-2-yl Me H H pyrazin-2-yl H H H H
benzo[b]thiophen-2-yl Me H H 3-methyl-pyrazin-2- H H H H
yl
benzo[b]thiophen-2-yl Me H H 3-methoxy-pyrazin- H H H H
2-yl
benzo[b]thiophen-2-yl Me H H 6-methyl-pyrazin-2- H H H H
yl
benzo[b]thiophen-2-yl Me H H 6-methoxy-pyrazin- H H H H
2-yl
benzo[b]thiophen-2-yl Me H F pyrazin-2-yl H H H H
benzo[b]thiophen-2-yl Me H H pyrimidin-2-yl H H H H
benzo[b]thiophen-2-yl Me H F pyrimidin-2-yl H H H H
benzo[b]thiophen-2-yl Me H H pyrimidin-4-yl H H H H
benzo[b]thiophen-2-yl Me H F pyrimidin-4-yl H H H H
benzo[b]thiophen-2-yl Me H H pyrimidin-5-yl H H H H
benzo[b]thiophen-2-yl Me H H pyrimidin-5-yl H F H H
benzo[b]thiophen-2-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
benzo[b]thiophen-2-yl Me H H thiazol-2-yl H H H H
benzo[b]thiophen-2-yl Me H H 5-methyl-thiazol-2- H H H H
yl
benzo[b]thiophen-2-yl Me H H [1,3,5]triazin-2-yl H H H H
benzo[b]thiophen-2-yl Me H H [1,2,4]triazin-3-yl H H H H
benzo[b]thiophen-2-yl Me H H [1,2,4]triazin-5-yl H H H H
benzo[b]thiophen-2-yl Me H H [1,2,4]triazin-6-yl H H H H
benzo[b]thiophen-2-yl Me H H cinnolin-3-yl H H H H
benzo[b]thiophen-2-yl Me H H phthalazin-1-yl H H H H
benzo[b]thiophen-2-yl Me H H quinoxalin-2-yl H H H H
benzo[b]thiophen-2-yl Me H H quinazolin-2-yl H H H H
benzo[b]thiophen-2-yl Me H H quinazolin-6-yl H H H H
benzo[b]thiophen-2-yl Me H H quinazolin-7-yl H H H H
benzo[b]thiophen-2-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
benzo[b]thiophen-2-yl Me H H morpholin-4-yl H H H H
4-fluoro-benzo[b]thiophen- Me H H morpholin-4-yl H H H H
2-yl
5-fluoro-benzo[b]thiophen- Me H H morpholin-4-yl H H H H
2-yl
6-fluoro-benzo[b]thiophen- Me H H morpholin-4-yl H H H H
2-yl
7-fluoro-benzo[b]thiophen- Me H H morpholin-4-yl H H H H
2-yl
benzo[b]thiophen-2-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
benzo[b]thiophen-2-yl Et H H morpholin-4-yl H H H H
benzo[b]thiophen-2-yl Me H F morpholin-4-yl H H H H
benzo[b]thiophen-2-yl Me H OMe morpholin-4-yl H H H H
benzo[b]thiophen-2-yl Me H OH morpholin-4-yl H H H H
benzo[b]thiophen-2-yl Me H Me morpholin-4-yl H H H H
benzo[b]thiophen-2-yl Et H F morpholin-4-yl H H H H
benzo[b]thiophen-2-yl Me H H morpholin-4-yl F H H H
benzo[b]thiophen-2-yl Me H H morpholin-4-yl H F H H
benzo[b]thiophen-2-yl Me H H morpholin-4-yl H H H OH
benzo[b]thiophen-2-yl Me H H morpholin-4-yl H H H Me
benzo[b]thiophen-2-yl Me H H piperazin-1-yl H H H H
benzo[b]thiophen-2-yl Me H H 4-methyl-piperazin- H H H H
1-yl
benzo[b]thiophen-2-yl Me H H piperidin-1-yl H H H H
benzo[b]thiophen-2-yl Me H H pyrrolidin-1-yl H H H H
benzo[b]thiophen-2-yl Me H H morpholin-4- H H H H
ylmethyl
benzo[b]thiophen-2-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
benzo[b]thiophen-2-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
benzo[b]thiophen-2-yl Me H H piperidin-1- H H H H
ylmethyl
benzo[b]thiophen-2-yl Me H H pyrrolidin-1- H H H H
ylmethyl
benzo[b]thiophen-2-yl Me H H CH2NMe2 H H H H
benzo[b]thiophen-2-yl Me H H 1-dimethylamino-1- H H H H
methylethyl
benzo[b]thiophen-2-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
benzo[b]thiophen-2-yl Me H H CH2NHMe H H H H
benzo[b]thiophen-2-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzo[b]thiophen-2-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzo[b]thiophen-2-yl Me H H CH2NH2 H H H H
benzo[b]thiophen-2-yl Me H H 1-amino-1- H H H H
methylethyl
benzo[b]thiophen-2-yl Me H H 1-amino- H H H H
cyclopropyl
benzo[b]thiophen-2-yl Me H H 2-oxo-2H-pyridin-1- H H H H
yl
benzo[b]thiophen-2-yl Me H H SO2CH3 H H H H
benzo[b]thiophen-2-yl Me H H CN H H H H
benzo[b]thiophen-2-yl Me H Me H H H H H
benzo[b]thiophen-3-yl Me H H H H H H H
benzo[b]thiophen-3-yl Me H H morpholin-4-yl H H H H
benzo[b]thiophen-3-yl Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-4-yl Me H H H H H H H
benzo[b]thiophen-4-yl Me H H morpholin-4-yl H H H H
benzo[b]thiophen-4-yl Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl H H H H H H H H
benzo[b]thiophen-5-yl H Me H H H H H H
benzo[b]thiophen-5-yl Me H H H H H H H
benzo[b]thiophen-5-yl Me H F H H H H H
benzo[b]thiophen-5-yl Me H OMe H H H H H
benzo[b]thiophen-5-yl Et H H H H H H H
benzo[b]thiophen-5-yl Me Me H H H H H H
2-methyl- Me H H H H H H H
benzo[b]thiophen-5-yl
2-chlorobenzo[b]thiophen- Me H H pyridazin-3-yl H H H H
5-yl
2-chlorobenzo[b]thiophen- Me H H pyrimidin-2-yl H H H H
5-yl
2-chlorobenzo[b]thiophen- Me H H pyrimidin-4-yl H H H H
5-yl
2-chlorobenzo[b]thiophen- Me H H pyrimidin-5-yl H H H H
5-yl
2-chlorobenzo[b]thiophen- Me H H pyrazin-2-yl H H H H
5-yl
2-chlorobenzo[b]thiophen- Me H H morpholin-4-yl H H H H
5-yl
3-trifluoromethyl- Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl
3-trifluoromethyl- Me H H pyrimidin-2-yl H H H H
benzo[b]thiophen-5-yl
3-trifluoromethyl- Me H H pyrimidin-4-yl H H H H
benzo[b]thiophen-5-yl
3-trifluoromethyl- Me H H pyrimidin-5-yl H H H H
benzo[b]thiophen-5-yl
3-trifluoromethyl- Me H H pyrazin-2-yl H H H H
benzo[b]thiophen-5-yl
3-trifluoromethyl- Me H H morpholin-4-yl H H H H
benzo[b]thiophen-5-yl
4-cyanobenzo[b]thiophen- Me H H H H H H H
5-yl
4- Me H H H H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Et H H pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H F pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Et H F pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H 6-methylpyridazin- H H H H
methoxybenzo[b]thiophen- 3-yl
5-yl
4- Me H H pyrimidin-2-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H pyrimidin-4-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H pyrimidin-5-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H pyrazin-2-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H morpholin-4-yl H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H H H OH H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H OH H H H H
methoxybenzo[b]thiophen-
5-yl
4- Me H H H H H H H
hydroxybenzo[b]thiophen-
5-yl
4- Et H H H H H H H
hydroxybenzo[b]thiophen-
5-yl
4- Et H H H H H H H
methoxybenzo[b]thiophen-
5-yl
1,1-dioxo-1H-1λ6- Me H H H H H H H
benzo[b]thiophen-5-yl
benzo[b]thiophen-5-yl Me H H H H H H OH
benzo[b]thiophen-5-yl Me H OMe H H H H OH
benzo[b]thiophen-5-yl Me H H F H H H OH
benzo[b]thiophen-5-yl Me H H H H H H OMe
benzo[b]thiophen-5-yl Me H H H H H H Me
benzo[b]thiophen-5-yl Me H H H H H H CN
benzo[b]thiophen-5-yl Me H H H H H H F
benzo[b]thiophen-5-yl Me H H H H H H Cl
benzo[b]thiophen-5-yl Me H H OH H H H H
benzo[b]thiophen-5-yl Me H H OMe H H H H
benzo[b]thiophen-5-yl Me H H Me H H H H
benzo[b]thiophen-5-yl Me H H F H H H H
benzo[b]thiophen-5-yl Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Et H H pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Me H H 6-methylpyridazin- H H H H
3-yl
benzo[b]thiophen-5-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
benzo[b]tbiophen-5-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
benzo[b]thiophen-5-yl Me H H 6-amino-pyridazin- H H H H
3-yl
benzo[b]thiophen-5-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
benzo[b]thiophen-5-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
benzo[b]thiophen-5-yl Me H H 6-cyano-pyridazin- H H H H
3-yl
benzo[b]thiophen-5-yl Me H F pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Me H OMe pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Me H OH pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Me H Me pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Et H F pyridazin-3-yl H H H H
benzo[b]thiophen-5-yl Me H H pyridazin-3-yl F H H H
benzo[b]thiophen-5-yl Me H H pyridazin-3-yl H F H H
benzo[b]thiophen-5-yl Me H H pyridazin-3-yl H H H OH
benzo[b]thiophen-5-yl Me H H pyridazin-3-yl H H H Me
benzo[b]thiophen-5-yl Me H H pyridazin-4-yl H H H H
benzo[b]thiophen-5-yl Me H F pyridazin-4-yl H H H H
benzo[b]thiophen-5-yl Me H H pyrazin-2-yl H H H H
benzo[b]thiophen-5-yl Me H H 3-methyl-pyrazin-2- H H H H
yl
benzo[b]thiophen-5-yl Me H H 3-methoxy-pyrazin- H H H H
2-yl
benzo[b]thiophen-5-yl Me H H 6-methyl-pyrazin-2- H H H H
yl
benzo[b]thiophen-5-yl Me H H 6-methoxy-pyrazin- H H H H
2-yl
benzo[b]thiophen-5-yl Me H F pyrazin-2-yl H H H H
benzo[b]thiophen-5-yl Me H OMe pyrazin-2-yl H H H H
benzo[b]thiophen-5-yl Me H OH pyrazin-2-yl H H H H
benzo[b]thiophen-5-yl Me H Me pyrazin-2-yl H H H H
benzo[b]thiophen-5-yl Me H H pyrimidin-2-yl H H H H
benzo[b]thiophen-5-yl Me H F pyrimidin-2-yl H H H H
benzo[b]thiophen-5-yl Me H OMe pyrimidin-2-yl H H H H
benzo[b]thiophen-5-yl Me H OH pyrimidin-2-yl H H H H
benzo[b]thiophen-5-yl Me H Me pyrimidin-2-yl H H H H
benzo[b]thiophen-5-yl Me H H pyrimidin-4-yl H H H H
benzo[b]thiophen-5-yl Me H F pyrimidin-4-yl H H H H
benzo[b]thiophen-5-yl Me H OMe pyrimidin-4-yl H H H H
benzo[b]thiophen-5-yl Me H OH pyrimidin-4-yl H H H H
benzo[b]thiophen-5-yl Me H Me pyrimidin-4-yl H H H H
benzo[b]thiophen-5-yl Me H H pyrimidin-5-yl H H H H
benzo[b]thiophen-5-yl Me H F pyrimidin-5-yl H H H H
benzo[b]thiophen-5-yl Me H OMe pyrimidin-5-yl H H H H
benzo[b]thiophen-5-yl Me H OH pyrimidin-5-yl H H H H
benzo[b]thiophen-5-yl Me H Me pyrimidin-5-yl H H H H
benzo[b]thiophen-5-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
benzo[b]thiophen-5-yl Me H H thiazol-2-yl H H H H
benzo[b]thiophen-5-yl Me H H 5-methyl-thiazol-2- H H H H
yl
benzo[b]thiophen-5-yl Me H H [1,3,5]triazin-2-yl H H H H
benzo[b]thiophen-5-yl Me H H [1,2,4]triazin-3-yl H H H H
benzo[b]thiophen-5-yl Me H H [1,2,4]triazin-5-yl H H H H
benzo[b]thiophen-5-yl Me H H [1,2,4]triazin-6-yl H H H H
benzo[b]thiophen-5-yl Me H H cinnolin-3-yl H H H H
benzo[b]thiophen-5-yl Me H H phthalazin-1-yl H H H H
benzo[b]tbiophen-5-yl Me H H quinoxalin-2-yl H H H H
benzo[b]thiophen-5-yl Me H H quinazolin-2-yl H H H H
benzo[b]thiophen-5-yl Me H H quinazolin-6-yl H H H H
benzo[b]thiophen-5-yl Me H H quinazolin-7-yl H H H H
benzo[b]thiophen-5-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
benzo[b]thiophen-5-yl Me H H morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
benzo[b]thiophen-5-yl Et H H morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Me H F morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Me H OMe morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Me H OH morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Me H Me morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Et H F morpholin-4-yl H H H H
benzo[b]thiophen-5-yl Me H H morpholin-4-yl F H H H
benzo[b]thiophen-5-yl Me H H morpholin-4-yl H F H H
benzo[b]thiophen-5-yl Me H H morpholin-4-yl H H H OH
benzo[b]thiophen-5-yl Me H H morpholin-4-yl H H H Me
benzo[b]thiophen-5-yl Me H H piperazin-1-yl H H H H
benzo[b]thiophen-5-yl Me H H 4-methyl-piperazin- H H H H
1-yl
benzo[b]thiophen-5-yl Me H H piperidin-1-yl H H H H
benzo[b]thiophen-5-yl Me H H pyrrolidin-1-yl H H H H
benzo[b]thiophen-5-yl Me H H morpholin-4- H H H H
ylmethyl
benzo[b]thiophen-5-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
benzo[b]thiophen-5-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
benzo[b]thiophen-5-yl Me H H piperidin-1- H H H H
ylmethyl
benzo[b]thiophen-5-yl Me H H pyrrolidin-1- H H H H
ylmethyl
benzo[b]thiophen-5-yl Me H H CH2NMe2 H H H H
benzo[b]thiophen-5-yl Me H H 1-dimethylamino-1- H H H H
methylethyl
benzo[b]thiophen-5-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
benzo[b]thiophen-5-yl Me H H CH2NHMe H H H H
benzo[b]thiophen-5-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzo[b]thiophen-5-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzo[b]thiophen-5-yl Me H H CH2NH2 H H H H
benzo[b]thiophen-5-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzo[b]thiophen-5-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzo[b]thiophen-5-yl Me H H 2-oxo-2H-pyridin-1- H H H H
yl
benzo[b]thiophen-5-yl Me H H SO2CH3 H H H H
benzo[b]thiophen-5-yl Me H H CN H H H H
benzo[b]thiophen-5-yl Me H F CN H H H H
benzo[b]thiophen-5-yl Me H Me H H H H H
benzo[b]thiophen-6-yl H H H H H H H H
benzo[b]thiophen-6-yl H Me H H H H H H
benzo[b]thiophen-6-yl Me H H H H H H H
benzo[b]thiophen-6-yl Me H F H H H H H
benzo[b]thiophen-6-yl Et H H H H H H H
benzo[b]thiophen-6-yl Me Me H H H H H H
2-methyl Me H H H H H H H
benzo[b]thiophen-6-yl
1,1-dioxo-1H-1λ6- Me H H H H H H H
benzo[b]thiophen-6-yl
benzo[b]thiophen-6-yl Me H H H H H H OH
benzo[b]thiophen-6-yl Me H H H H H H OMe
benzo[b]thiophen-6-yl Me H H H H H H Me
benzo[b]thiophen-6-yl Me H H H H H H CN
benzo[b]tbiophen-6-yl Me H H H H H H F
benzo[b]thiophen-6-yl Me H H H H H H Cl
2-chlorobenzo[b]thiophen- Me H H pyridazin-3-yl H H H H
6-yl
2-chlorobenzo[b]thiophen- Me H H pynmidm-2-yl H H H H
6-yl
2-chlorobenzo[b]thiophen- Me H H pyrimidin-4-yl H H H H
6-yl
2-chlorobenzo[b]thiophen- Me H H pyrimidin-5-yl H H H H
6-yl
2-chlorobenzo[b]thiophen- Me H H pyrazin-2-yl H H H H
6-yl
2-chlorobenzo[b]thiophen- Me H H morpholin-4-yl H H H H
6-yl
3-trifluoromethyl- Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl
3-trifluoromethyl- Me H H pyrimidin-2-yl H H H H
benzo[b]thiophen-6-yl
3-trifluoromethyl- Me H H pyrimidin-4-yl H H H H
benzo[b]thiophen-6-yl
3-trifluoromethyl- Me H H pyrimidin-5-yl H H H H
benzo[b]thiophen-6-yl
3-trifluoromethyl- Me H H pyrazin-2-yl H H H H
benzo[b]thiophen-6-yl
3-trifluoromethyl- Me H H morpholin-4-yl H H H H
benzo[b]thiophen-6-yl
7- Me H H H H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H H pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Et H H pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H F pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Et H F pyridazin-3-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H H 6-methylpyridazin- H H H H
methoxybenzo[b]thiophen- 3-yl
6-yl
7- Me H H pyrimidin-2-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H H pyrimidin-4-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H H pyrimidin-5-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H H pyrazin-2-yl H H H H
methoxybenzo[b]thiophen-
6-yl
7- Me H H morpholin-4-yl H H H H
methoxybenzo[b]tbiophen-
6-yl
7- Me H H OH H H H H
methoxybenzo[b]thiophen-
6-yl
benzo[b]thiophen-6-yl Me H H OH H H H H
benzo[b]thiophen-6-yl Me H H OMe H H H H
benzo[b]thiophen-6-yl Me H H Me H H H H
benzo[b]thiophen-6-yl Me H H F H H H H
benzo[b]thiophen-6-yl Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Et H H pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Me H H 6-methylpyridazin- H H H H
3-yl
benzo[b]thiophen-6-yl Me H H 6-dimethylamino- H H H H
pyridazine-3-yl
benzo[b]thiophen-6-yl Me H H 6-methylamino- H H H H
pyridazine-3-yl
benzo[b]thiophen-6-yl Me H H 6-amino-pyridazine- H H H H
3-yl
benzo[b]thiophen-6-yl Me H H 6-morpholin-4-yl- H H H H
pyridazine-3-yl
benzo[b]thiophen-6-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
benzo[b]thiophen-6-yl Me H H 6-cyano-pyridazine- H H H H
3-yl
benzo[b]thiophen-6-yl Me H F pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Me H OMe pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Me H OH pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Me H Me pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Et H F pyridazin-3-yl H H H H
benzo[b]thiophen-6-yl Me H H pyridazin-3-yl F H H H
benzo[b]thiophen-6-yl Me H H pyridazin-3-yl H F H H
benzo[b]thiophen-6-yl Me H H pyridazin-3-yl H H H OH
benzo[b]thiophen-6-yl Me H H pyridazin-3-yl H H H Me
benzo[b]thiophen-6-yl Me H H pyridazin-4-yl H H H H
benzo[b]thiophen-6-yl Me H F pyridazin-4-yl H H H H
benzo[b]thiophen-6-yl Me H H pyrazin-2-yl H H H H
benzo[b]thiophen-6-yl Me H H 3-methyl-pyrazin-2- H H H H
yl
benzo[b]thiophen-6-yl Me H H 3-methoxy-pyrazin- H H H H
2-yl
benzo[b]thiophen-6-yl Me H H 6-methyl-pyrazin-2- H H H H
yl
benzo[b]thiophen-6-yl Me H H 6-methoxy-pyrazin- H H H H
2-yl
benzo[b]thiophen-6-yl Me H F pyrazin-2-yl H H H H
benzo[b]thiophen-6-yl Me H OMe pyrazin-2-yl H H H H
benzo[b]thiophen-6-yl Me H OH pyrazin-2-yl H H H H
benzo[b]thiophen-6-yl Me H Me pyrazin-2-yl H H H H
benzo[b]thiophen-6-yl Me H H pyrimidin-2-yl H H H H
benzo[b]thiophen-6-yl Me H F pyrimidin-2-yl H H H H
benzo[b]thiophen-6-yl Me H OMe pyrimidin-2-yl H H H H
benzo[b]thiophen-6-yl Me H OH pyrimidin-2-yl H H H H
benzo[b]thiophen-6-yl Me H Me pyrimidin-2-yl H H H H
benzo[b]thiophen-6-yl Me H H pyrimidin-4-yl H H H H
benzo[b]thiophen-6-yl Me H F pyrimidin-4-yl H H H H
benzo[b]thiophen-6-yl Me H OMe pyrimidin-4-yl H H H H
benzo[b]thiophen-6-yl Me H OH pyrimidin-4-yl H H H H
benzo[b]thiophen-6-yl Me H Me pyrimidin-4-yl H H H H
benzo[b]thiophen-6-yl Me H H pyrimidin-5-yl H H H H
benzo[b]thiophen-6-yl Me H F pyrimidin-5-yl H H H H
benzo[b]thiophen-6-yl Me H OMe pyrimidin-5-yl H H H H
benzo[b]thiophen-6-yl Me H OH pyrimidin-5-yl H H H H
benzo[b]thiophen-6-yl Me H Me pyrimidin-5-yl H H H H
benzo[b]thiophen-6-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
benzo[b]thiophen-6-yl Me H H thiazol-2-yl H H H H
benzo[b]thiophen-6-yl Me H H 5-methyl-thiazol-2- H H H H
yl
benzo[b]thiophen-6-yl Me H H [1,3,5]triazin-2-yl H H H H
benzo[b]thiophen-6-yl Me H H [1,2,4]triazin-3-yl H H H H
benzo[b]thiophen-6-yl Me H H [1,2,4]triazin-5-yl H H H H
benzo[b]thiophen-6-yl Me H H [1,2,4]triazin-6-yl H H H H
benzo[b]thiophen-6-yl Me H H cinnolin-3-yl H H H H
benzo[b]thiophen-6-yl Me H H phthalazin-1-yl H H H H
benzo[b]thiophen-6-yl Me H H quinoxalin-2-yl H H H H
benzo[b]thiophen-6-yl Me H H quinazolin-2-yl H H H H
benzo[b]thiophen-6-yl Me H H quinazolin-6-yl H H H H
benzo[b]thiophen-6-yl Me H H quinazolin-7-yl H H H H
benzo[b]thiophen-6-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
benzo[b]thiophen-6-yl Me H H morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
benzo[b]thiophen-6-yl Et H H morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Me H F morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Me H OMe morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Me H OH morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Me H Me morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Et H F morpholin-4-yl H H H H
benzo[b]thiophen-6-yl Me H H morpholin-4-yl F H H H
benzo[b]thiophen-6-yl Me H H morpholin-4-yl H F H H
benzo[b]thiophen-6-yl Me H H morpholin-4-yl H H H OH
benzo[b]thiophen-6-yl Me H H morpholin-4-yl H H H Me
benzo[b]thiophen-6-yl Me H H piperazin-1-yl H H H H
benzo[b]thiophen-6-yl Me H H 4-methyl-piperazin- H H H H
1-yl
benzo[b]thiophen-6-yl Me H H piperidin-1-yl H H H H
benzo[b]thiophen-6-yl Me H H pyrrolidin-l-yl H H H H
benzo[b]thiophen-6-yl Me H H morpholin-4- H H H H
ylmethyl
benzo[b]thiophen-6-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
benzo[b]thiophen-6-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
benzo[b]thiophen-6-yl Me H H piperidin-1- H H H H
ylmethyl
benzo[b]thiophen-6-yl Me H H pyrrolidin-1- H H H H
ylmethyl
benzo[b]thiophen-6-yl Me H H CH2NMe2 H H H H
benzo[b]thiophen-6-yl Me H H 1-dimethylamino-1- H H H H
methylethyl
benzo[b]thiophen-6-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
benzo[b]thiophen-6-yl Me H H CH2NHMe H H H H
benzo[b]thiophen-6-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzo[b]thiophen-6-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzo[b]thiophen-6-yl Me H H CH2NH2 H H H H
benzo[b]thiophen-6-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzo[b]thiophen-6-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzo[b]thiophen-6-yl Me H H 2-oxo-2H-pyridin-1- H H H H
yl
benzo[b]thiophen-6-yl Me H H SO2CH3 H H H H
benzo[b]thiophen-6-yl Me H H CN H H H H
benzo[b]thiophen-6-yl Me H F CN H H H H
benzo[b]thiophen-6-yl Me H Me H H H H H
benzo[b]thiophen-7-yl Me H H H H H H H
benzo[b]thiophen-7-yl Et H H H H H H H
benzo[b]thiophen-7-yl Me H F H H H H H
benzo[b]thiophen-7-yl Et H F H H H H H
benzo[b]thiophen-7-yl Me H H pyridazin-3-yl H H H H
benzo[b]thiophen-7-yl Me H H morpholin-4-yl H H H H
benzo[b]thiophen-5-yl S1a H H H H H H H
benzo[b]thiophen-5-yl S2a H H H H H H H
benzo[b]thiophen-5-yl S3a H H H H H H H
benzo[b]thiophen-5-yl S4a H H H H H H H
benzo[b]thiophen-5-yl S5a H H H H H H H
benzo[b]thiophen-5-yl Me H H H H H H S6a
aS1 = cyclopropyl
S2 = cyanomethyl
S3 = 2-dimethylaminoethyl
S4 = 2-hydroxyethyl
S5 = isopropyl
S6 = morpholin-4-yl

wherein the carbon atom designated * is in the R or S configuration. That is, the specific compounds herein include:

  • 4-(benzo[b]thiophen-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-fluoro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-fluoro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-fluoro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-chloro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-chloro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-chloro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-chloro-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxy-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-methoxy-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-methoxy-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1,1-dioxo-1H-1λ6-benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-ol;
  • 4-(benzo[b]thiophen-2-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-(benzo[b]thiophen-2-yl)-4-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-4-chloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2,5-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(benzo[b]thiophen-2-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-ethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(6-methylpyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-benzo [b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl-carbonitrile;
  • 4-benzo[b]thiophen-2-yl-8-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-2-yl-2,8-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-ethyl-8-fluoro-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-6-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-5-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-2-yl-2,4-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-8-fluoro-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-8-fluoro-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-8-fluoro-2-methyl-7-pyrimidin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-8-fluoro-2-methyl-7-pyrimidin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-7-(3 ,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(thiazol-2-yl)-I,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-[1,3 ,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-benzo[b]thiophen-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-ethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo [b]thiophen-2-yl-8-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo [b]thiophen-2-yl-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-ethyl-8-fluoro-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-6-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-5-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-2-yl-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-piperazin-1-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-morpholin-4-ylmethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-7-piperidin-1-ylmethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-2-yl)-2-methyl-7-pyrrolidin-1-ylmethyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(benzo[b]thiophen-2-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzo[b]thiophen-2-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-3-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-3-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-3-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-4-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-4-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-methyl-benzo[b]thiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chlorobenzo[b]thiophen-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chlorobenzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chlorobenzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chlorobenzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chlorobenzo[b]thiophen-5-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chlorobenzo[b]thiophen-5-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyridazin-3-yl-4-(3-trifluoromethyl-benzo [b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrimidin-2-yl -4-(3-trifluoromethyl-benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrimidin-4-yl -4-(3-trifluoromethyl-benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrimidin-5-yl -4-(3-trifluoromethyl-benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrazin-2-yl-4-(3-trifluoromethyl-benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-morpholin-4-yl-4-(3-trifluoromethyl-benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 5-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzo[b]thiophene-4-carbonitrile;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(4-methoxybenzo[b]thiophen-5-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(4-methoxybenzo[b]thiophen-5-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxybenzo[b]thiophen-5-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-methoxy-benzo[b]thiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-5-ol;
  • 4-(4-methoxy-benzo[b]thiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 5-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzo[b]thiophen-4-ol;
  • 5-(2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzo[b]thiophen-4-ol;
  • 2-ethyl-4-(4-methoxy-benzo[b]thiophen-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1,1-dioxo-1H-1λ6-benzo[b]thiophen-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-5-yl-8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-5-yl-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzo[b]thiophen-5-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-(benzo[b]thiophen-5-yl)-4-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-4-chloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(benzo[b]thiophen-5-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-ethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-benzo [b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-benzo [b]thiophen-5-yl-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 4-benzo[b]thiophen-5-yl-8-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-5-yl-2,8-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-ethyl-8-fluoro-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-6-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-5-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-5-yl-2,4-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-8-fluoro-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-methoxy-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-5-yl-2,8-dimethyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-fluoro-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-methoxy-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-5-yl-2,8-dimethyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-8-fluoro-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-8-methoxy-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzo[b]thiophen-5-yl)-2,8-dimethyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-8-fluoro-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-8-methoxy-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzo[b]thiophen-5-yl)-2,8-dimethyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-[1,3,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-ethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-5-yl-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-ethyl-8-fluoro-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-6-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-5-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-5-yl-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-piperazin-1-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-5-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-benzo [b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)methylamine;
  • 1-(4-benzo[b]thiophen-5-yl-2-methy-1,1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-benzo [b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(benzo[b]thiophen-5-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-benzo[b]thiophen-5-yl-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzo[b]thiophen-5-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-4-(2-methyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1,1-dioxo-1H-1λ6-benzo[b]thiophen-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzo[b]thiophen-6-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-(benzo[b]thiophen-6-yl)-4-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-4-chloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chloro-benzo[b]thiophen-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chloro-benzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chloro-benzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chloro-benzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chloro-benzo[b]thiophen-6-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2-chloro-benzo[b]thiophen-6-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyridazin-3-yl-4-(3-trifluoromethyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrimidin-2-yl -4-(3-trifluoromethyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrimidin-4-yl -4-(3-trifluoromethyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrimidin-5-yl -4-(3-trifluoromethyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-pyrazin-2-yl-4-(3-trifluoromethyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-7-morpholin-4-yl-4-(3-trifluoromethyl-benzo[b]thiophen-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(7-methoxybenzo[b]thiophen-6-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(7-methoxybenzo[b]thiophen-6-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxybenzo[b]thiophen-6-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzo[b]thiophen-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-ol;
  • 4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol; (benzo[b]thiophen-6-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo [b]thiophen-6-yl-2-ethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylaamine;
  • 6-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 4-benzo[b]thiophen-6-yl-8-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-6-yl-2,8-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-ethyl-8-fluoro-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-6-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-5-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-6-yl-2,4-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-8-fluoro-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-Benzo[b]thiophen-6-yl-8-methoxy-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-6-yl-2,8-dimethyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-8-fluoro-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-8-methoxy-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-6-yl-2,8-dimethyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-8-fluoro-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-8-methoxy-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzo[b]thiophen-6-yl)-2,8-dimethyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-8-fluoro-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-8-methoxy-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzo[b]thiophen-6-yl)-2,8-dimethyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-[1,3,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo [b]thiophen-6-yl-7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-ethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-8-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-benzo[b]thiophen-6-yl-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-ethyl-8-fluoro-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-6-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-5-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzo[b]thiophen-6-yl-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-piperazin-1-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo [b]thiophen-6-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-6-yl-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-benzo[b]thiophen-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(benzo[b]thiophen-6-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-benzo[b]thiophen-6-yl-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzo[b]thiophen-6-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-7-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-7-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-7-yl)-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-7-yl)-2-ethyl-8-fluoro-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-7-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo[b]thiophen-7-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-cyclopropyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-benzo[b]thiophen-5-yl-3,4-dihydro-1H-isoquinolin-2-yl)-acetonitrile;
  • [2-(4-benzo[b]thiophen-5-yl-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-dimethylamine;
  • 2-(4-benzo[b]thiophen-5-yl-3,4-dihydro-1H-isoquinolin-2-yl)-ethanol;
  • 4-benzo[b]thiophen-5-yl-2-isopropyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzo[b]thiophen-5-yl-2-methyl-8-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • or an oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a prodrug thereof.

In addition, other specific compounds of the present invention are those with the following substituents:

TABLE B
X R1 R2 R3 R4 R5 R6 R7 R8
benzofuran-2-yl H H H H H H H H
benzofuran-2-yl H Me H H H H H H
benzofuran-2-yl Me H H H H H H H
benzofuran-2-yl Et H H H H H H H
benzofuran-2-yl Me Me H H H H H H
5-chloro-benzofuran-2-yl Me H H H H H H H
5-fluoro-benzofuran-2-yl Me H H H H H H H
7-fluoro-benzofuran-2-yl Me H H H H H H H
5-methoxy-benzofuran-2-yl Me H H H H H H H
7-methoxy-benzofuran-2-yl Me H H H H H H H
7-methoxy-benzofuran-2-yl Me H H pyridazin-3-yl H H H H
7-methoxy-benzofuran-2-yl Me H F pyridazin-3-yl H H H H
7-methoxy-benzofuran-2-yl Me H H morpholin-4-yl H H H H
7-methoxy-benzofuran-2-yl Me H F morpholin-4-yl H H H H
benzofuran-2-yl Me H H H H H H OH
benzofuran-2-yl Me H H H H H H OMe
benzofuran-2-yl Me H H H H H H Me
benzofuran-2-yl Me H H H H H H CN
benzofuran-2-yl Me H H H H H H F
benzofuran-2-yl Me H H H H H H Cl
benzofuran-2-yl Me H H H H Me H H
benzofuran-2-yl Me H H OH H H H H
benzofuran-2-yl Me H H OMe H H H H
benzofuran-2-yl Me H H Me H H H H
benzofuran-2-yl Me H H F H H H H
benzofuran-2-yl Me H H pyridazin-3-yl H H H H
4-fluoro-benzofuran-2-yl Me H H pyridazin-3-yl H H H H
5-fluoro-benzofuran-2-yl Me H H pyridazin-3-yl H H H H
6-fluoro-benzofuran-2-yl Me H H pyridazin-3-yl H H H H
7-fluoro-benzofuran-2-yl Me H H pyridazin-3-yl H H H H
benzofuran-2-yl Et H H pyridazin-3-yl H H H H
benzofuran-2-yl Me H H 6- H H H H
methylpyridazin-
3-yl
benzofuran-2-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
benzofuran-2-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
benzofuran-2-yl Me H H 6-amino- H H H H
pyridazin-3-yl
benzofuran-2-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
benzofuran-2-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
benzofuran-2-yl Me H H 6-cyano- H H H H
pyridazin-3-yl
benzofuran-2-yl Me H F pyridazin-3-yl H H H H
benzofuran-2-yl Me H OMe pyridazin-3-yl H H H H
benzofuran-2-yl Me H OH pyridazin-3-yl H H H H
benzofuran-2-yl Me H Me pyridazin-3-yl H H H H
benzofuran-2-yl Et H F pyridazin-3-yl H H H H
benzofuran-2-yl Me H H pyridazin-3-yl F H H H
benzofuran-2-yl Me H H pyridazin-3-yl H F H H
benzofuran-2-yl Me H H pyridazin-3-yl H H H OH
benzofuran-2-yl Me H H pyridazin-3-yl H H H Me
benzofuran-2-yl Me H H pyridazin-4-yl H H H H
benzofuran-2-yl Me H F pyridazin-4-yl H H H H
benzofuran-2-yl Me H H pyrazin-2-yl H H H H
benzofuran-2-yl Me H H 3-methyl-pyrazin- H H H H
2-yl
benzofuran-2-yl Me H H 3-methoxy- H H H H
pyrazin-2-yl
benzofuran-2-yl Me H H 6-methyl-pyrazin- H H H H
2-yl
benzofuran-2-yl Me H H 6-methoxy- H H H H
pyrazin-2-yl
benzofuran-2-yl Me H F pyrazin-2-yl H H H H
benzofuran-2-yl Me H H pyrimidin-2-yl H H H H
benzofuran-2-yl Me H F pyrimidin-2-yl H H H H
benzofuran-2-yl Me H H pyrimidin-4-yl H H H H
benzofuran-2-yl Me H F pyrimidin-4-yl H H H H
benzofuran-2-yl Me H H pyrimidin-5-yl H H H H
benzofuran-2-yl Me H F pyrimidin-5-yl H H H H
benzofuran-2-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
benzofuran-2-yl Me H H thiazol-2-yl H H H H
benzofuran-2-yl Me H H 5-methyl-thiazol- H H H H
2-yl
benzofuran-2-yl Me H H [1,3,5]triazin-2-yl H H H H
benzofuran-2-yl Me H H [1,2,4]triazin-3-yl H H H H
benzofuran-2-yl Me H H [1,2,4]triazin-5-yl H H H H
benzofuran-2-yl Me H H [1,2,4]triazin-6-yl H H H H
benzofuran-2-yl Me H H cinnolin-3-yl H H H H
benzofuran-2-yl Me H H phthalazin-1-yl H H H H
benzofuran-2-yl Me H H quinoxalin-2-yl H H H H
benzofuran-2-yl Me H H quinazolin-2-yl H H H H
benzofuran-2-yl Me H H quinazolin-6-yl H H H H
benzofuran-2-yl Me H H quinazolin-7-yl H H H H
benzofuran-2-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
benzofuran-2-yl Me H H morpholin-4-yl H H H H
4-fluoro-benzofuran-2-yl Me H H morpholin-4-yl H H H H
5-fluoro-benzofuran-2-yl Me H H morpholin-4-yl H H H H
6-fluoro-benzofuran-2-yl Me H H morpholin-4-yl H H H H
7-fluoro-benzofuran-2-yl Me H H morpholin-4-yl H H H H
benzofuran-2-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
benzofuran-2-yl Et H H morpholin-4-yl H H H H
benzofuran-2-yl Me H F morpholin-4-yl H H H H
benzofuran-2-yl Et H F morpholin-4-yl H H H H
benzofuran-2-yl Me H H morpholin-4-yl F H H H
benzofuran-2-yl Me H H morpholin-4-yl H F H H
benzofuran-2-yl Me H OMe morpholin-4-yl H H H H
benzofuran-2-yl Me H OH morpholin-4-yl H H H H
benzofuran-2-yl Me H Me morpholin-4-yl H H H H
benzofuran-2-yl Me H H morpholin-4-yl H H H OH
benzofuran-2-yl Me H H morpholin-4-yl H H H Me
benzofuran-2-yl Me H H piperazin-1-yl H H H H
benzofuran-2-yl Me H H 4-methyl- H H H H
piperazin-1-yl
benzofuran-2-yl Me H H piperidin-1-yl H H H H
benzofuran-2-yl Me H H pyrrolidin-1-yl H H H H
benzofuran-2-yl Me H H morpholin-4- H H H H
ylmethyl
benzofuran-2-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
benzofuran-2-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
benzofuran-2-yl Me H H piperidin-1- H H H H
ylmethyl
benzofuran-2-yl Me H H pyrrolidin-1- H H H H
ylmethyl
benzofuran-2-yl Me H H CH2NMe2 H H H H
benzofuran-2-yl Me H H 1-dimethylamino- H H H H
1-methylethyl
benzofuran-2-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
benzofuran-2-yl Me H H CH2NHMe H H H H
benzofuran-2-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzofuran-2-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzofuran-2-yl Me H H CH2NH2 H H H H
benzofuran-2-yl Me H H 1-amino-1- H H H H
methylethyl
benzofuran-2-yl Me H H 1-amino- H H H H
cyclopropyl
benzofuran-2-yl Me H H 2-oxo-2H- H H H H
pyridin-1-yl
benzofuran-2-yl Me H H SO2CH3 H H H H
benzofuran-2-yl Me H H CN H H H H
benzofuran-2-yl Me H Me H H H H H
benzofuran-3-yl Me H H H H H H H
benzofuran-3-yl Me H H morpholin-4-yl H H H H
benzofuran-3-yl Me H H pyridazin-3-yl H H H H
benzofuran-4-yl Me H H H H H H H
benzofuran-4-yl Me H H morpholin-4-yl H H H H
benzofuran-4-yl Me H H pyridazin-3-yl H H H H
benzofuran-5-yl H H H H H H H H
benzofuran-5-yl H Me H H H H H H
benzofuran-5-yl Me H H H H H H H
benzofuran-5-yl Me H F H H H H H
benzofuran-5-yl Et H H H H H H H
benzofuran-5-yl Me Me H H H H H H
3-methyl-benzofuran-5-yl Me H H H H H H H
benzofuran-5-yl Me H H H H H H OH
benzofuran-5-yl Me H H H H H H OMe
benzofuran-5-yl Me H H H H H H Me
benzofuran-5-yl Me H H H H H H CN
benzofuran-5-yl Me H H H H H H F
benzofuran-5-yl Me H H H H H H Cl
benzofuran-5-yl Me H H OH H H H H
benzofuran-5-yl Me H H OMe H H H H
benzofuran-5-yl Me H H Me H H H H
benzofuran-5-yl Me H H F H H H H
benzofuran-5-yl Me H H pyridazin-3-yl H H H H
benzofuran-5-yl Et H H pyridazin-3-yl H H H H
benzofuran-5-yl Me H H 6- H H H H
methylpyridazin-
3-yl
benzofuran-5-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
benzofuran-5-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
benzofuran-5-yl Me H H 6-amino- H H H H
pyridazin-3-yl
benzofuran-5-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
benzofuran-5-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
benzofuran-5-yl Me H H 6-cyano- H H H H
pyridazin-3-yl
benzofuran-5-yl Me H F pyridazin-3-yl H H H H
benzofuran-5-yl Me H OMe pyridazin-3-yl H H H H
benzofuran-5-yl Me H OH pyridazin-3-yl H H H H
benzofuran-5-yl Me H Me pyridazin-3-yl H H H H
benzofuran-5-yl Et H F pyridazin-3-yl H H H H
benzofuran-5-yl Me H H pyridazin-3-yl F H H H
benzofuran-5-yl Me H H pyridazin-3-yl H F H H
benzofuran-5-yl Me H H pyridazin-3-yl H H H OH
benzofuran-5-yl Me H H pyridazin-3-yl H H H Me
benzofuran-5-yl Me H H pyridazin-4-yl H H H H
benzofuran-5-yl Me H F pyridazin-4-yl H H H H
benzofuran-5-yl Me H H pyrazin-2-yl H H H H
benzofuran-5-yl Me H H 3-methyl-pyrazin- H H H H
2-yl
benzofuran-5-yl Me H H 3-methoxy- H H H H
pyrazin-2-yl
benzofuran-5-yl Me H H 6-methyl-pyrazin- H H H H
2-yl
benzofuran-5-yl Me H H 6-methoxy- H H H H
pyrazin-2-yl
benzofuran-5-yl Me H F pyrazin-2-yl H H H H
benzofuran-5-yl Me H OMe pyrazin-2-yl H H H H
benzofuran-5-yl Me H OH pyrazin-2-yl H H H H
benzofuran-5-yl Me H Me pyrazin-2-yl H H H H
benzofuran-5-yl Me H H pyrimidin-2-yl H H H H
benzofuran-5-yl Me H F pyrimidin-2-yl H H H H
benzofuran-5-yl Me H OMe pyrimidin-2-yl H H H H
benzofuran-5-yl Me H OH pyrimidin-2-yl H H H H
benzofuran-5-yl Me H Me pyrimidin-2-yl H H H H
benzofuran-5-yl Me H H pyrimidin-4-yl H H H H
benzofuran-5-yl Me H F pyrimidin-4-yl H H H H
benzofuran-5-yl Me H OMe pyrimidin-4-yl H H H H
benzofuran-5-yl Me H OH pyrimidin-4-yl H H H H
benzofuran-5-yl Me H Me pyrimidin-4-yl H H H H
benzofuran-5-yl Me H H pyrimidin-5-yl H H H H
benzofuran-5-yl Me H F pyrimidin-5-yl H H H H
benzofuran-5-yl Me H OMe pyrimidin-5-yl H H H H
benzofuran-5-yl Me H OH pyrimidin-5-yl H H H H
benzofuran-5-yl Me H Me pyrimidin-5-yl H H H H
benzofiiran-5-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
benzofuran-5-yl Me H H thiazol-2-yl H H H H
benzofuran-5-yl Me H H 5-methyl-thiazol- H H H H
2-yl
benzofuran-5-yl Me H H [1,3,5]triazin-2-yl H H H H
benzofuran-5-yl Me H H [1,2,4]triazin-3-yl H H H H
benzofuran-5-yl Me H H [1,2,4]triazin-5-yl H H H H
benzofuran-5-yl Me H H [1,2,4]triazin-6-yl H H H H
benzofuran-5-yl Me H H cinnolin-3-yl H H H H
benzofuran-5-yl Me H H phthalazin-1-yl H H H H
benzofuran-5-yl Me H H quinoxalin-2-yl H H H H
benzofuran-5-yl Me H H quinazolin-2-yl H H H H
benzofuran-5-yl Me H H quinazolin-6-yl H H H H
benzofuran-5-yl Me H H quinazolin-7-yl H H H H
benzofuran-5-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
benzofuran-5-yl Me H H morpholin-4-yl H H H H
benzofuran-5-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
benzofuran-5-yl Et H H morpholin-4-yl H H H H
benzofuran-5-yl Me H F morpholin-4-yl H H H H
benzofuran-5-yl Me H OMe morpholin-4-yl H H H H
benzofuran-5-yl Me H OH morpholin-4-yl H H H H
benzofuran-5-yl Me H Me morpholin-4-yl H H H H
benzofuran-5-yl Et H F morpholin-4-yl H H H H
benzofuran-5-yl Me H H morpholin-4-yl F H H H
benzofuran-5-yl Me H H morpholin-4-yl H F H H
benzofuran-5-yl Me H H morpholin-4-yl H H H OH
benzofuran-5-yl Me H H morpholin-4-yl H H H Me
benzofuran-5-yl Me H H piperidin-1-yl H H H H
benzofuran-5-yl Me H H pyrrolidin-1-yl H H H H
benzofuran-5-yl Me H H morpholin-4- H H H H
ylmethyl
benzofuran-5-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
benzofuran-5-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
benzofuran-5-yl Me H H piperidin-1- H H H H
ylmethyl
benzofuran-5-yl Me H H pyrrolidin-1- H H H H
ylmethyl
benzofuran-5-yl Me H H CH2NMe2 H H H H
benzofuran-5-yl Me H H 1-dimethylamino- H H H H
1-methylethyl
benzofuran-5-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
benzofuran-5-yl Me H H CH2NHMe H H H H
benzofuran-5-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzofuran-5-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzofuran-5-yl Me H H CH2NH2 H H H H
benzofuran-5-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzofuran-5-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzofuran-5-yl Me H H 2-oxo-2H- H H H H
pyridin-1-yl
benzofuran-5-yl Me H H SO2CH3 H H H H
benzofuran-5-yl Me H H CN H H H H
benzofuran-5-yl Me H F CN H H H H
benzofuran-5-yl Me H Me H H H H H
2,3-dihydrobenzofuran-5-yl Me H H H H H H H
benzofuran-6-yl H H H H H H H H
benzofuran-6-yl H Me H H H H H H
benzofuran-6-yl Me H H H H H H H
benzofuran-6-yl Et H H H H H H H
benzofuran-6-yl Me Me H H H H H H
benzofuran-6-yl Me H H H H H H OH
benzofuran-6-yl Me H H H H H H OMe
benzofuran-6-yl Me H H H H H H Me
benzofuran-6-yl Me H H H H H H CN
benzofuran-6-yl Me H H H H H H F
benzofuran-6-yl Me H H H H H H Cl
benzofuran-6-yl Me H H OH H H H H
benzofuran-6-yl Me H H OMe H H H H
benzofuran-6-yl Me H H Me H H H H
benzofuran-6-yl Me H H F H H H H
benzofuran-6-yl Me H H pyridazin-3-yl H H H H
benzofuran-6-yl Et H H pyridazin-3-yl H H H H
benzofuran-6-yl Me H H 6- H H H H
methylpyridazin-
3-yl
benzofuran-6-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
benzofuran-6-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
benzofuran-6-yl Me H H 6-amino- H H H H
pyridazin-3-yl
benzofuran-6-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
benzofuran-6-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
benzofuran-6-yl Me H H 6-cyano- H H H H
pyridazin-3-yl
benzofuran-6-yl Me H F pyridazin-3-yl H H H H
benzofuran-6-yl Me H OMe pyridazin-3-yl H H H H
benzofuran-6-yl Me H OH pyridazin-3-yl H H H H
benzofuran-6-yl Me H Me pyridazin-3-yl H H H H
benzofuran-6-yl Et H F pyridazin-3-yl H H H H
benzofuran-6-yl Me H H pyridazin-3-yl F H H H
benzofuran-6-yl Me H H pyridazin-3-yl H F H H
benzofuran-6-yl Me H H pyridazin-4-yl H H H H
benzofuran-6-yl Me H F pyridazin-4-yl H H H H
benzofuran-6-yl Me H H pyrazin-2-yl H H H H
benzofuran-6-yl Me H H 3-methyl-pyrazin- H H H H
2-yl
benzofuran-6-yl Me H H 3-methoxy- H H H H
pyrazin-2-yl
benzofuran-6-yl Me H H 6-methyl-pyrazin- H H H H
2-yl
benzofuran-6-yl Me H H 6-methoxy- H H H H
pyrazin-2-yl
benzofuran-6-yl Me H F pyrazin-2-yl H H H H
benzofuran-6-yl Me H OMe pyrazin-2-yl H H H H
benzofuran-6-yl Me H OH pyrazin-2-yl H H H H
benzofuran-6-yl Me H Me pyrazin-2-yl H H H H
benzofuran-6-yl Me H H pyrimidin-2-yl H H H H
benzofuran-6-yl Me H F pyrimidin-2-yl H H H H
benzofuran-6-yl Me H OMe pyrimidin-2-yl H H H H
benzofuran-6-yl Me H OH pyrimidin-2-yl H H H H
benzofuran-6-yl Me H Me pyrimidin-2-yl H H H H
benzofuran-6-yl Me H H pyrimidin-4-yl H H H H
benzofuran-6-yl Me H F pyrimidin-4-yl H H H H
benzofuran-6-yl Me H OMe pyrimidin-4-yl H H H H
benzofuran-6-yl Me H OH pyrimidin-4-yl H H H H
benzofuran-6-yl Me H Me pyrimidin-4-yl H H H H
benzofuran-6-yl Me H H pyrimidin-5-yl H H H H
benzofuran-6-yl Me H F pyrimidin-5-yl H H H H
benzofuran-6-yl Me H OMe pyrimidin-5-yl H H H H
benzofuran-6-yl Me H OH pyrimidin-5-yl H H H H
benzofuran-6-yl Me H Me pyrimidin-5-yl H H H H
benzofuran-6-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
benzofuran-6-yl Me H H thiazol-2-yl H H H H
benzofuran-6-yl Me H H 5-methyl-thiazol- H H H H
2-yl
benzofuran-6-yl Me H H [1,3,5]triazin-2-yl H H H H
benzofuran-6-yl Me H H [1,2,4]triazin-3-yl H H H H
benzofuran-6-yl Me H H [1,2,4]triazin-5-yl H H H H
benzofuran-6-yl Me H H [1,2,4]triazin-6-yl H H H H
benzofuran-6-yl Me H H cinnolin-3-yl H H H H
benzofuran-6-yl Me H H phthalazin-1-yl H H H H
benzofuran-6-yl Me H H quinoxalin-2-yl H H H H
benzofuran-6-yl Me H H quinazolin-2-yl H H H H
benzofuran-6-yl Me H H quinazolin-6-yl H H H H
benzofuran-6-yl Me H H quinazolin-7-yl H H H H
benzofuran-6-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
benzofuran-6-yl Me H H morpholin-4-yl H H H H
benzofuran-6-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
benzofuran-6-yl Et H H morpholin-4-yl H H H H
benzofuran-6-yl Me H F morpholin-4-yl H H H H
benzofuran-6-yl Me H OMe morpholin-4-yl H H H H
benzofuran-6-yl Me H OH morpholin-4-yl H H H H
benzofuran-6-yl Me H Me morpholin-4-yl H H H H
benzofuran-6-yl Et H F morpholin-4-yl H H H H
benzofuran-6-yl Me H H morpholin-4-yl F H H H
benzofuran-6-yl Me H H morpholin-4-yl H F H H
benzofuran-6-yl Me H H morpholin-4-yl H H H OH
benzofuran-6-yl Me H H morpholin-4-yl H H H Me
benzofuran-6-yl Me H H piperidin-1-yl H H H H
benzofuran-6-yl Me H H pyrrolidin-1-yl H H H H
benzofuran-6-yl Me H H morpholin-4- H H H H
ylmethyl
benzofuran-6-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
benzofuran-6-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
benzofuran-6-yl Me H H piperidin-1- H H H H
ylmethyl
benzofuran-6-yl Me H H pyrrolidin-1- H H H H
ylmethyl
benzofuran-6-yl Me H H CH2NMe2 H H H H
benzofuran-6-yl Me H H 1-dimethylamino- H H H H
1-methylethyl
benzofuran-6-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
benzofuran-6-yl Me H H CH2NHMe H H H H
benzofuran-6-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzofuran-6-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzofuran-6-yl Me H H CH2NH2 H H H H
benzofuran-6-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
benzofuran-6-yl Me H H 1-methylamino- H H H H
cyclopropyl
benzofuran-6-yl Me H H 2-oxo-2H- H H H H
pyridin-1-yl
benzofuran-6-yl Me H H SO2CH3 H H H H
benzofuran-6-yl Me H H CN H H H H
benzofuran-6-yl Me H F CN H H H H
benzofuran-6-yl Me H Me H H H H H
benzofuran-7-yl Me H H H H H H H
benzofuran-7-yl Et H H H H H H H
benzofuran-7-yl Me H F H H H H H
benzofuran-7-yl Et H F H H H H H
benzofuran-7-yl Me H H pyridazin-3-yl H H H H
benzofuran-7-yl Me H H morpholin-4-yl H H H H

wherein the carbon atom designated * is in the R or S configuration. That is, the specific compounds herein include:

  • 4-(benzofuran-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-chloro-benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-fluoro-benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-methoxy-benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzofuran-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzofuran-2-yl)-8-fluoro-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-benzofuran-2-yl)-8-fluoro-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzofuran-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-benzofuran-2-yl-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzofuran-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-(benzofuran-2-yl)-4-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-4-chloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2,5-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzo furan-2-yl)-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-fluoro-benzofuran-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-fluoro-benzofuran-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-fluoro-benzofuran-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-benzofuran-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-ethyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-(benzo furan-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(benzofuran-2-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 4-(benzofuran-2-yl)-8-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-2-yl)-2,8-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-ethyl-8-fluoro-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-6-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-5-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-2-yl)-2,4-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-8-fluoro-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-8-fluoro-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-8-fluoro-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-8-fluoro-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-8-fluoro-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-[1,3,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(4-fluoro-benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-fluoro-benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-fluoro-benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-ethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-8-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-2-yl)-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-ethyl-8-fluoro-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-6-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-5-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-2-yl)-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzofuran-2-yl-2-methyl-7-piperazin-1-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzofuran-2-yl-2-methyl-7-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylaamine;
  • 1-(4-benzofuran-2-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(benzofuran-2-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzofuran-2-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-3-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-3-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-3-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-4-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-4-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(3-methyl-benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzofuran-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-5-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-(benzofuran-5-yl)-4-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-4-chloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(benzofuran-5-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-ethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 6-4-(benzofuran-5-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-4-(benzofuran-5-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-ethyl-8-fluoro-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-6-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-5-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-5-yl)-2,4-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-methoxy-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline
  • 4-(benzofuran-5-yl)-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-((benzofuran-5-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-methoxy-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-((benzofuran-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-methoxy-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-methoxy-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-[1,3,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(benzofuran-5-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-ethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-ethyl-8-fluoro-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-6-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-5-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-5-yl)-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(benzofuran-5-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzofuran-5-yl)-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzofuran-5-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(2,3-dihydrobenzofuran-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-benzofuran-6-yl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-6-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-(benzofuran-6-yl)-4-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-4-chloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(benzofuran-6-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-7-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-ethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(benzofuran-6-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 4-(benzofuran-6-yl)-8-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-6-yl)-2,8-dimethyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-ethyl-8-fluoro-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-6-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-5-fluoro-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-8-fluoro-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-methoxy-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline
  • 4-(benzofuran-6-yl)-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-6-yl)-2,8-dimethyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-fluoro-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-methoxy-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-6-yl)-2,8-dimethyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-8-fluoro-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-8-methoxy-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-6-yl-)-2,8-dimethyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-8-fluoro-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-8-methoxy-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-6-yl-)-2,8-dimethyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-[1,3,5]triazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-[1,2,4]triazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-[1,2,4]triazin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-[1,2,4]triazin-6-yl-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-7-(2,6-dimethyl-morpholin-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-ethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(benzofuran-6-yl)-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-ethyl-8-fluoro-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-6-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-5-fluoro-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(benzofuran-6-yl)-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-(benzofuran-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(benzofuran-6-yl-)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-6-yl-)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzofuran-6-yl)-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(benzofuran-6-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-7-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-7-yl)-2-ethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-7-yl)-8-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-7-yl)-2-ethyl-8-fluoro-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-7-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(benzofuran-7-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • or an oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a prodrug thereof.

In addition, other specific compounds of the present invention are those with the following substituents:

TABLE C
X R1 R2 R3 R4 R5 R6 R7 R8
indol-1-yl Me H H H H H H H
1H-indol-2-yl H H H H H H H H
1H-indol-2-yl H Me H H H H H H
1H-indol-2-yl Me H H H H H H H
1H-indol-2-yl Et H H H H H H H
1H-indol-2-yl Me Me H H H H H H
5-methoxy-1H- Me H H H H H H H
indol-2-yl
1H-indol-2-yl Me H H H H H H OH
1H-indol-2-yl Me H H H H H H OMe
1H-indol-2-yl Me H H H H H H Me
1H-indol-2-yl Me H H H H H H CN
1H-indol-2-yl Me H H H H H H F
1H-indol-2-yl Me H H H H H H Cl
1H-indol-2-yl Me H H OH H H H H
1H-indol-2-yl Me H H OMe H H H H
1H-indol-2-yl Me H H Me H H H H
1H-indol-2-yl Me H H F H H H H
1H-indol-2-yl Me H H pyridazin-3-yl H H H H
1-methyl-1H-indol- Me H H pyridazin-3-yl H H H H
2-yl
7-fluoro-1H-indol- Me H H pyridazin-3-yl H H H H
2-yl
1H-indol-2-yl Et H H pyridazin-3-yl H H H H
1H-indol-2-yl Me H H 6-methylpyridazin- H H H H
3-yl
1H-indol-2-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
1H-indol-2-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
1H-indol-2-yl Me H H 6-amino-pyridazin- H H H H
3-yl
1H-indol-2-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
1H-indol-2-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
1H-indol-2-yl Me H H 6-cyano-pyridazin- H H H H
3-yl
1H-indol-2-yl Me H F pyridazin-3-yl H H H H
1H-indol-2-yl Et H F pyridazin-3-yl H H H H
1H-indol-2-yl Me H H pyridazin-3-yl F H H H
1H-indol-2-yl Me H H pyridazin-3-yl H F H H
1H-indol-2-yl Me H OMe pyridazin-3-yl H H H H
1H-indol-2-yl Me H OH pyridazin-3-yl H H H H
1H-indol-2-yl Me H Me pyridazin-3-yl H H H H
1H-indol-2-yl Me H H pyridazin-3-yl H H H OH
1H-indol-2-yl Me H H pyridazin-3-yl H H H Me
1H-indol-2-yl Me H H pyridazin-4-yl H H H H
1H-indol-2-yl Me H F pyridazin-4-yl H H H H
1H-indol-2-yl Me H H pyrazin-2-yl H H H H
1H-indol-2-yl Me H H 3-methyl-pyrazin-2- H H H H
yl
1H-indol-2-yl Me H H 3-methoxy-pyrazin- H H H H
2-yl
1H-indol-2-yl Me H H 6-methyl-pyrazin-2- H H H H
yl
1H-indol-2-yl Me H H 6-methoxy-pyrazin- H H H H
2-yl
1H-indol-2-yl Me H F pyrazin-2-yl H H H H
1H-indol-2-yl Me H H pyrimidin-2-yl H H H H
1H-indol-2-yl Me H F pyrimidin-2-yl H H H H
1H-indol-2-yl Me H H pyrimidin-4-yl H H H H
1H-indol-2-yl Me H F pyrimidin-4-yl H H H H
1H-indol-2-yl Me H H pyrimidin-5-yl H H H H
1H-indol-2-yl Me H F pyrimidin-5-yl H H H H
1H-indol-2-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
1H-indol-2-yl Me H H thiazol-2-yl H H H H
1H-indol-2-yl Me H H 5-methyl-thiazol-2- H H H H
yl
1H-indol-2-yl Me H H cinnolin-3-yl H H H H
1H-indol-2-yl Me H H phthalazin-1-yl H H H H
1H-indol-2-yl Me H H quinoxalin-2-yl H H H H
1H-indol-2-yl Me H H quinazolin-2-yl H H H H
1H-indol-2-yl Me H H quinazolin-6-yl H H H H
1H-indol-2-yl Me H H quinazolin-7-yl H H H H
1H-indol-2-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
1H-indol-2-yl Me H H morpholin-4-yl H H H H
1-methyl-indol-2-yl Me H H morpholin-4-yl H H H H
7-fluoro-1H-indol- Me H H morpholin-4-yl H H H H
2-yl
1H-indol-2-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
1H-indol-2-yl Et H H morpholin-4-yl H H H H
1H-indol-2-yl Me H F morpholin-4-yl H H H H
1H-indol-2-yl Et H F morpholin-4-yl H H H H
1H-indol-2-yl Me H H morpholin-4-yl F H H H
1H-indol-2-yl Me H H morpholin-4-yl H F H H
1H-indol-2-yl Me H OMe morpholin-4-yl H H H H
1H-indol-2-yl Me H OH morpholin-4-yl H H H H
1H-indol-2-yl Me H Me morpholin-4-yl H H H H
1H-indol-2-yl Me H H morpholin-4-yl H H H OH
1H-indol-2-yl Me H H morpholin-4-yl H H H Me
1H-indol-2-yl Me H H piperidin-1-yl H H H H
1H-indol-2-yl Me H H pyrrolidin-1-yl H H H H
1H-indol-2-yl Me H H morpholin-4- H H H H
ylmethyl
1H-indol-2-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
1H-indol-2-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
1H-indol-2-yl Me H H piperidin-1- H H H H
ylmethyl
1H-indol-2-yl Me H H pyrrolidin-1- H H H H
ylmethyl
1H-indol-2-yl Me H H CH2NMe2 H H H H
1H-indol-2-yl Me H H 1-dimethylamino-1- H H H H
methylethyl
1H-indol-2-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
1H-indol-2-yl Me H H CH2NHMe H H H H
1H-indol-2-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
1H-indol-2-yl Me H H 1-methylamino- H H H H
cyclopropyl
1H-indol-2-yl Me H H CH2NH2 H H H H
1H-indol-2-yl Me H H 1-amino-1- H H H H
methylethyl
1H-indol-2-yl Me H H 1-amino- H H H H
cyclopropyl
1H-indol-2-yl Me H H 2-oxo-2H-pyridin-1- H H H H
yl
1H-indol-2-yl Me H H SO2CH3 H H H H
1H-indol-2-yl Me H H CN H H H H
1H-indol-2-yl Me H Me H H H H H
1H-indol-3-yl Me H H H H H H H
1H-indol-4-yl Me H H H H H H H
1H-indol-5-yl H H H H H H H H
1H-indol-5-yl H Me H H H H H H
1H-indol-5-yl Me H H H H H H H
1H-indol-5-yl Et H H H H H H H
1H-indol-5-yl Me Me H H H H H H
1H-indol-5-yl Me H H H H H H OH
1H-indol-5-yl Me H H H H H H OMe
1H-indol-5-yl Me H H H H H H Me
1H-indol-5-yl Me H H H H H H CN
1H-indol-5-yl Me H H H H H H F
1H-indol-5-yl Me H H H H H H Cl
1H-indol-5-yl Me H H OH H H H H
1H-indol-5-yl Me H H OMe H H H H
1H-indol-5-yl Me H H Me H H H H
1H-indol-5-yl Me H H F H H H H
1H-indol-5-yl Me H H pyridazin-3-yl H H H H
1-methyl-indol-5-yl Me H H pyridazin-3-yl H H H H
7-fluoro-1H-indol- Me H H pyridazin-3-yl H H H H
5-yl
1H-indol-5-yl Et H H pyridazin-3-yl H H H H
1H-indol-5-yl Me H H 6-methylpyridazin- H H H H
3-yl
1H-indol-5-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
1H-indol-5-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
1H-indol-5-yl Me H H 6-amino-pyridazin- H H H H
3-yl
1H-indol-5-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
1H-indol-5-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
1H-indol-5-yl Me H H 6-cyano-pyridazin- H H H H
3-yl
1H-indol-5-yl Me H F pyridazin-3-yl H H H H
1H-indol-5-yl Et H F pyridazin-3-yl H H H H
1H-indol-5-yl Me H H pyridazin-3-yl F H H H
1H-indol-5-yl Me H H pyridazin-3-yl H F H H
1H-indol-5-yl Me H OMe pyridazin-3-yl H H H H
1H-indol-5-yl Me H OH pyridazin-3-yl H H H H
1H-indol-5-yl Me H Me pyridazin-3-yl H H H H
1H-indol-5-yl Me H H pyridazin-3-yl H H H OH
1H-indol-5-yl Me H H pyridazin-3-yl H H H Me
1H-indol-5-yl Me H H pyridazin-4-yl H H H H
1H-indol-5-yl Me H F pyridazin-4-yl H H H H
1H-indol-5-yl Me H H pyrazin-2-yl H H H H
1H-indol-5-yl Me H H 3-methyl-pyrazin-2- H H H H
yl
1H-indol-5-yl Me H H 3-methoxy-pyrazin- H H H H
2-yl
1H-indol-5-yl Me H H 6-methyl-pyrazin-2- H H H H
yl
1H-indol-5-yl Me H H 6-methoxy-pyrazin- H H H H
2-yl
1H-indol-5-yl Me H H pyrazin-2-yl H F H H
1H-indol-5-yl Me H H pyrimidin-2-yl H H H H
1H-indol-5-yl Me H F pyrimidin-2-yl H H H H
1H-indol-5-yl Me H H pyrimidin-4-yl H H H H
1H-indol-5-yl Me H F pyrimidin-4-yl H H H H
1H-indol-5-yl Me H H pyrimidin-5-yl H H H H
1H-indol-5-yl Me H F pyrimidin-5-yl H H H H
1H-indol-5-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
1H-indol-5-yl Me H H thiazol-2-yl H H H H
1H-indol-5-yl Me H H 5-methyl-thiazol-2- H H H H
yl
1H-indol-5-yl Me H H cinnolin-3-yl H H H H
1H-indol-5-yl Me H H phthalazin-1-yl H H H H
1H-indol-5-yl Me H H quinoxalin-2-yl H H H H
1H-indol-5-yl Me H H quinazolin-2-yl H H H H
1H-indol-5-yl Me H H quinazolin-6-yl H H H H
1H-indol-5-yl Me H H quinazolin-7-yl H H H H
1H-indol-5-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
1H-indol-5-yl Me H H morpholin-4-yl H H H H
1-methyl-indol-5-yl Me H H morpholin-4-yl H H H H
7-fluoro-1H-indol- Me H H morpholin-4-yl H H H H
5-yl
1H-indol-5-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
1H-indol-5-yl Et H H morpholin-4-yl H H H H
1H-indol-5-yl Me H F morpholin-4-yl H H H H
1H-indol-5-yl Et H F morpholin-4-yl H H H H
1H-indol-5-yl Me H H morpholin-4-yl F H H H
1H-indol-5-yl Me H H morpholin-4-yl H F H H
1H-indol-5-yl Me H OMe morpholin-4-yl H H H H
1H-indol-5-yl Me H OH morpholin-4-yl H H H H
1H-indol-5-yl Me H Me morpholin-4-yl H H H H
1H-indol-5-yl Me H H morpholin-4-yl H H H OH
1H-indol-5-yl Me H H morpholin-4-yl H H H Me
1H-indol-5-yl Me H H piperidin-1-yl H H H H
1H-indol-5-yl Me H H pyrrolidin-1-yl H H H H
1H-indol-5-yl Me H H morpholin-4- H H H H
ylmethyl
1H-indol-5-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
1H-indol-5-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
1H-indol-5-yl Me H H piperidin-1- H H H H
ylmethyl
1H-indol-5-yl Me H H pyrrolidin-1- H H H H
ylmethyl
1H-indol-5-yl Me H H CH2NMe2 H H H H
1H-indol-5-yl Me H H 1-dimethylamino-1- H H H H
methylethyl
1H-indol-5-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
1H-indol-5-yl Me H H CH2NHMe H H H H
1H-indol-5-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
1H-indol-5-yl Me H H 1-methylamino- H H H H
cyclopropyl
1H-indol-5-yl Me H H CH2NH2 H H H H
1H-indol-5-yl Me H H 1-amino-1- H H H H
methylethyl
1H-indol-5-yl Me H H 1-amino- H H H H
cyclopropyl
1H-indol-5-yl Me H H 2-oxo-2H-pyridin-1- H H H H
yl
1H-indol-5-yl Me H H SO2CH3 H H H H
1H-indol-5-yl Me H H CN H H H H
1H-indol-5-yl Me H Me H H H H H
1-benzyl-1H-indol- Me H H H H H H H
5-yl
1H-indol-6-yl H H H H H H H H
1H-indol-6-yl H Me H H H H H H
1H-indol-6-yl Me H H H H H H H
3-chloro-1H-indol- Me H H H H H H H
6-yl
1H-indol-6-yl Et H H H H H H H
1H-indol-6-yl Me Me H H H H H H
1H-indol-6-yl Me H H H H H H OH
1H-indol-6-yl Me H H H H H H OMe
1H-indol-6-yl Me H H H H H H Me
1H-indol-6-yl Me H H H H H H CN
1H-indol-6-yl Me H H H H H H F
1H-indol-6-yl Me H H H H H H Cl
1H-indol-6-yl Me H H OH H H H H
1H-indol-6-yl Me H H OMe H H H H
1H-indol-6-yl Me H H Me H H H H
1H-indol-6-yl Me H H F H H H H
1H-indol-6-yl Me H H pyridazin-3-yl H H H H
1-methyl-indol-6-yl Me H H pyridazin-3-yl H H H H
7-fluoro-1H-indol- Me H H pyridazin-3-yl H H H H
6-yl
1H-indol-6-yl Et H H pyridazin-3-yl H H H H
1H-indol-6-yl Me H H 6-methylpyridazin- H H H H
3-yl
1H-indol-6-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
1H-indol-6-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
1H-indol-6-yl Me H H 6-amino-pyridazin- H H H H
3-yl
1H-indol-6-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
1H-indol-6-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
1H-indol-6-yl Me H H 6-cyano-pyridazin- H H H H
3-yl
1H-indol-6-yl Me H F pyridazin-3-yl H H H H
1H-indol-6-yl Et H F pyridazin-3-yl H H H H
1H-indol-6-yl Me H H pyridazin-3-yl F H H H
1H-indol-6-yl Me H H pyridazin-3-yl H F H H
1H-indol-6-yl Me H OMe pyridazin-3-yl H H H H
1H-indol-6-yl Me H OH pyridazin-3-yl H H H H
1H-indol-6-yl Me H Me pyridazin-3-yl H H H H
1H-indol-6-yl Me H H pyridazin-3-yl H H H OH
1H-indol-6-yl Me H H pyridazin-3-yl H H H Me
1H-indol-6-yl Me H H pyridazin-4-yl H H H H
1H-indol-6-yl Me H F pyridazin-4-yl H H H H
1H-indol-6-yl Me H H pyrazin-2-yl H H H H
1H-indol-6-yl Me H H 3-methyl-pyrazin-2- H H H H
yl
1H-indol-6-yl Me H H 3-methoxy-pyrazin- H H H H
2-yl
1H-indol-6-yl Me H H 6-methyl-pyrazin-2- H H H H
yl
1H-indol-6-yl Me H H 6-methoxy-pyrazin- H H H H
2-yl
1H-indol-6-yl Me H F pyrazin-2-yl H H H H
1H-indol-6-yl Me H H pyrimidin-2-yl H H H H
1H-indol-6-yl Me H F pyrimidin-2-yl H H H H
1H-indol-6-yl Me H H pyrimidin-4-yl H H H H
1H-indol-6-yl Me H F pyrimidin-4-yl H H H H
1H-indol-6-yl Me H H pyrimidin-5-yl H H H H
1H-indol-6-yl Me H F pyrimidin-5-yl H H H H
1H-indol-6-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
1H-indol-6-yl Me H H thiazol-2-yl H H H H
1H-indol-6-yl Me H H 5-methyl-thiazol-2- H H H H
yl
1H-indol-6-yl Me H H cinnolin-3-yl H H H H
1H-indol-6-yl Me H H phthalazin-1-yl H H H H
1H-indol-6-yl Me H H quinoxalin-2-yl H H H H
1H-indol-6-yl Me H H quinazolin-2-yl H H H H
1H-indol-6-yl Me H H quinazolin-6-yl H H H H
1H-indol-6-yl Me H H quinazolin-7-yl H H H H
1H-indol-6-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
1H-indol-6-yl Me H H morpholin-4-yl H H H H
1-methyl-indol-6-yl Me H H morpholin-4-yl H H H H
7-fluoro-1H-indol- Me H H morpholin-4-yl H H H H
6-yl
1H-indol-6-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
1H-indol-6-yl Et H H morpholin-4-yl H H H H
1H-indol-6-yl Me H F morpholin-4-yl H H H H
1H-indol-6-yl Et H F morpholin-4-yl H H H H
1H-indol-6-yl Me H H morpholin-4-yl F H H H
1H-indol-6-yl Me H H morpholin-4-yl H F H H
1H-indol-6-yl Me H OMe morpholin-4-yl H H H H
1H-indol-6-yl Me H OH morpholin-4-yl H H H H
1H-indol-6-yl Me H Me morpholin-4-yl H H H H
1H-indol-6-yl Me H H morpholin-4-yl H H H OH
1H-indol-6-yl Me H H morpholin-4-yl H H H Me
1H-indol-6-yl Me H H piperidin-1-yl H H H H
1H-indol-6-yl Me H H pyrrolidin-1-yl H H H H
1H-indol-6-yl Me H H morpholin-4- H H H H
ylmethyl
1H-indol-6-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
1H-indol-6-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
1H-indol-6-yl Me H H piperidin-1- H H H H
ylmethyl
1H-indol-6-yl Me H H pyrrolidin-1- H H H H
ylmethyl
1H-indol-6-yl Me H H CH2NMe2 H H H H
1H-indol-6-yl Me H H 1-dimethylamino-1- H H H H
methylethyl
1H-indol-6-yl Me H H 1-dimethylamino- H H H H
cyclopropyl
1H-indol-6-yl Me H H CH2NHMe H H H H
1H-indol-6-yl Me H H 1-methyl-1- H H H H
methylaminoethyl
1H-indol-6-yl Me H H 1-methylamino- H H H H
cyclopropyl
1H-indol-6-yl Me H H CH2NH2 H H H H
1H-indol-6-yl Me H H 1-amino-1- H H H H
methylethyl
1H-indol-6-yl Me H H 1-amino- H H H H
cyclopropyl
1H-indol-6-yl Me H H 2-oxo-2H-pyridin-1- H H H H
yl
1H-indol-6-yl Me H H SO2CH3 H H H H
1H-indol-6-yl Me H H CN H H H H
1H-indol-6-yl Me H Me H H H H H
1-methyl-1H-indol- Me H H H H H H H
5-yl
1-methyl-1H-indol- Me H F H H H H H
5-yl
1-methyl-1H-indol- Et H F H H H H H
5-yl
1-benzyl-1H-indol- Me H H H H H H H
5-yl
(3-cyano-benzyl)- Me H H H H H H H
1H-indol-5-yl
(2-cyano-benzyl)- Me H H H H H H H
1H-indol-5-yl
1-methyl-1H-indol- Me H H H H H H H
6-yl
1-methyl-1H-indol- Me H F H H H H H
6-yl
1-methyl-1H-indol- Et H F H H H H H
6-yl
1-benzyl-1H-indol- Me H H H H H H H
6-yl
(3-cyano-benzyl)- Me H H H H H H H
1H-indol-6-yl
(2-cyano-benzyl)- Me H H H H H H H
1H-indol-6-yl

wherein the carbon atom designated * is in the R or S configuration. That is, the specific compounds herein include:

  • 4-(1H-indol-1-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 1,2-dimethyl-4-(1H-indol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(5-methoxy-1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(1H-indol-2-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-fluoro-4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-chloro-4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(1H-indol-2-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,7-dimethyl-4-(1H-indol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 7-fluoro-4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-1H-indol-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indol-2-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-2-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(6-methylpyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(1H-indol-2-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 8-fluoro-4-(1H-indol-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indol-2-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indol-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indol-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 2,8-dimethyl-4-(1H-indol-2-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 2,4-dimethyl-4-(1H-indol-2-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-2-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-2-yl)-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-2-yl)-2-methyl-7-pyrimidin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-2-yl)-2-methyl-7-pyrimidin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(1H-indol-2-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 7-(2,6-dimethyl-morpholin-4-yl)-4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-2-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indol-2-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 4-(1H-indol-2-yl)-2,8-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(1H-indol-2-yl)-2,4-dimethyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(1H-indol-2-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 2,8-dimethyl-4-(1H-indol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-3-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 1,2-dimethyl-4-(1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(1H-indol-5-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-fluoro-4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-chloro-4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(1H-indol-5-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,7-dimethyl-4-(1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 7-fluoro-4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-indol-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indol-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-5-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(6-methylpyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(1H-indol-5-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 8-fluoro-4-(1H-indol-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indol-5-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indol-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indol-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 2,8-dimethyl-4-(1H-indol-5-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 2,4-dimethyl-4-(1H-indol-5-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-5-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-8-fluoro-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-5-yl)-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-5-yl)-2-methyl-7-pyrimidin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-5-yl)-2-methyl-7-pyrimidin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(1H-indol-5-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 7-(2,6-dimethyl-morpholin-4-yl)-4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 2,8-dimethyl-4-(1H-indol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 2,4-dimethyl-4-(1H-indol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(1H-indol-5-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(1H-indol-5-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-benzyl-1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(3-chloro-1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 1,2-dimethyl-4-(1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(1H-indol-6-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,4-dimethyl-4-(1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-fluoro-4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-chloro-4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(1H-indol-6-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,7-dimethyl-4-(1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 7-fluoro-4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-indol-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indol-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-6-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(1H-indol-6-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 6-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazine-3-carbonitrile;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indol-6-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-8-methoxy-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 2,8-dimethyl-4-(1H-indol-6-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 2,4-dimethyl-4-(1H-indol-6-yl)-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(3-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-7-(3-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(6-methyl-pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-7-(6-methoxy-pyrazin-2-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyrazin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyrimidin-2-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyrimidin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-pyrimidin-5-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(1H-indol-6-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 7-(2,6-dimethyl-morpholin-4-yl)-4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indol-6-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indol-6-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 2,8-dimethyl-4-(1H-indol-6-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 2,4-dimethyl-4-(1H-indol-6-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(morpholin-4-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(piperidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-7-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroisoquinoline;
  • (4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-dimethylamine;
  • [1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-dimethylamine;
  • [1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-dimethylamine;
  • (4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)-methylamine;
  • [1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethyl]-methylamine;
  • [1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropyl]-methylamine;
  • C-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-methylamine;
  • 1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-methyl-ethylamine;
  • 1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cyclopropylamine;
  • 1-(4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1 H-pyridin-2-one;
  • 4-(1H-indol-6-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 2,8-dimethyl-4-(1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-4-(1-methyl-1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-2-methyl-4-(1-methyl-1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1-methyl-1H-indol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-benzyl-1H-indol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 3-[5-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-indol-1-ylmethyl]-benzonitrile;
  • 2-[5-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-indol-1-ylmethyl]-benzonitrile;
  • 2-methyl-4-(1-methyl-1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-2-methyl-4-(1-methyl-1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1-methyl-1H-indol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-benzyl-1H-indol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 3-[6-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-indol-1-ylmethyl]-benzonitrile;
  • 2-[6-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-indol-1-ylmethyl]-benzonitrile;
  • or an oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a prodrug thereof

Other specific compounds of the present invention are those with the following substituents:

TABLE D
X R1 R2 R3 R4 R5 R6 R7 R8
indazol-1-yl Me H H H H H H H
1H-indazol-3-yl Me H H H H H H H
1H-indazol-4-yl Me H H H H H H H
1H-indazol-5-yl H H H H H H H H
1H-indazol-5-yl H Me H H H H H H
1H-indazol-5-yl Me H H H H H H H
1-methyl-1H-indazol- Me H H H H H H H
5-yl
6-methoxy-1H- Me H H H H H H H
indazol-5-yl
7-methoxy-1H- Me H H H H H H H
indazol-5-yl
7-fluoro-1H-indazol- Me H H H H H H H
5-yl
7-chloro-1H-indazol- Me H H H H H H H
5-yl
7-methyl-1H-indazol- Me H H H H H H H
5-yl
1H-indazol-5-yl Me H F H H H H H
1H-indazol-5-yl Et H H H H H H H
1H-indazol-5-yl Et H F H H H H H
1H-indazol-5-yl Me Me H H H H H H
1H-indazol-5-yl Me H H H H H H OH
1H-indazol-5-yl Me H H H H H H OMe
1H-indazol-5-yl Me H H H H H H Me
1H-indazol-5-yl Me H H H H H H CN
1H-indazol-5-yl Me H H H H H H F
1H-indazol-5-yl Me H H H H H H Cl
1H-indazol-5-yl Me H H OH H H H H
1H-indazol-5-yl Me H H OMe H H H H
1H-indazol-5-yl Me H H Me H H H H
1H-indazol-5-yl Me H H F H H H H
1H-indazol-5-yl Me H H pyridazin-3-yl H H H H
1-methyl-indazol-5-yl Me H H pyridazin-3-yl H H H H
7-fluoro-1H-indazol- Me H H pyridazin-3-yl H H H H
5-yl
1H-indazol-5-yl Et H H pyridazin-3-yl H H H H
1H-indazol-5-yl Me H H 6- H H H H
methylpyridazin-
3-yl
1H-indazol-5-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
1H-indazol-5-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
1H-indazol-5-yl Me H H 6-amino- H H H H
pyridazin-3-yl
1H-indazol-5-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
1H-indazol-5-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
1H-indazol-5-yl Me H H pyridazin-4-yl H H H H
1H-indazol-5-yl Me H H pyrazin-2-yl H H H H
1H-indazol-5-yl Me H H pyrimidin-2-yl H H H H
1H-indazol-5-yl Me H H pyrimidin-4-yl H H H H
1H-indazol-5-yl Me H H pyrimidin-5-yl H H H H
1H-indazol-5-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
1H-indazol-5-yl Me H H thiazol-2-yl H H H H
1H-indazol-5-yl Me H H 5-methyl-thiazol- H H H H
2-yl
1H-indazol-5-yl Me H H cinnolin-3-yl H H H H
1H-indazol-5-yl Me H H phthalazin-1-yl H H H H
1H-indazol-5-yl Me H H quinoxalin-2-yl H H H H
1H-indazol-5-yl Me H H quinazolin-2-yl H H H H
1H-indazol-5-yl Me H H quinazolin-6-yl H H H H
1H-indazol-5-yl Me H H quinazolin-7-yl H H H H
1H-indazol-5-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
1H-indazol-5-yl Me H H morpholin-4-yl H H H H
1-methyl-1H-indazol- Me H H morpholin-4-yl H H H H
5-yl
7-fluoro-1H-indazol- Me H H morpholin-4-yl H H H H
5-yl
1H-indazol-5-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
1H-indazol-5-yl Et H H morpholin-4-yl H H H H
1H-indazol-5-yl Me H F morpholin-4-yl H H H H
1H-indazol-5-yl Et H F morpholin-4-yl H H H H
1H-indazol-5-yl Me H H morpholin-4-yl F H H H
1H-indazol-5-yl Me H H morpholin-4-yl H F H H
1H-indazol-5-yl Me H OMe morpholin-4-yl H H H H
1H-indazol-5-yl Me H OH morpholin-4-yl H H H H
1H-indazol-5-yl Me H Me morpholin-4-yl H H H H
1H-indazol-5-yl Me H H morpholin-4-yl H H H OH
1H-indazol-5-yl Me H H morpholin-4-yl H H H Me
1H-indazol-5-yl Me H H piperidin-1-yl H H H H
1H-indazol-5-yl Me H H pyrrolidin-1-yl H H H H
1H-indazol-5-yl Me H H morpholin-4- H H H H
ylmethyl
1H-indazol-5-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
1H-indazol-5-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
1H-indazol-5-yl Me H H piperidin-1- H H H H
ylmethyl
1H-indazol-5-yl Me H H pyrrolidin-1- H H H H
ylmethyl
1H-indazol-5-yl Me H H CH2NMe2 H H H H
1H-indazol-5-yl Me H H CH2NHMe H H H H
1H-indazol-5-yl Me H H 2-oxo-2H-pyridin- H H H H
1-yl
1H-indazol-5-yl Me H H SO2CH3 H H H H
1H-indazol-5-yl Me H H CN H H H H
1H-indazol-5-yl Me H Me H H H H H
1-methyl-1H-indazol- Me H F H H H H H
5-yl
1-methyl-1H-indazol- Et H F H H H H H
5-yl
1-benzyl-1H-indazol- Me H H H H H H H
5-yl
(3-cyano-benzyl)-1H- Me H H H H H H H
indazol-5-yl
(2-cyano-benzyl)-1H- Me H H H H H H H
indazol-5-yl
1H-indazol-6-yl H H H H H H H H
1H-indazol-6-yl H Me H H H H H H
1H-indazol-6-yl Me H H H H H H H
1-methyl-indazol-6-yl Me H H H H H H H
7-fluoro-1H-indazol- Me H H H H H H H
6-yl
1H-indazol-6-yl Et H H H H H H H
1H-indazol-6-yl Me Me H H H H H H
1H-indazol-6-yl Me H H H H H H OH
1H-indazol-6-yl Me H H H H H H OMe
1H-indazol-6-yl Me H H H H H H Me
1H-indazol-6-yl Me H H H H H H CN
1H-indazol-6-yl Me H H H H H H F
1H-indazol-6-yl Me H H H H H H Cl
1H-indazol-6-yl Me H H OH H H H H
1H-indazol-6-yl Me H H OMe H H H H
1H-indazol-6-yl Me H H Me H H H H
1H-indazol-6-yl Me H H F H H H H
1H-indazol-6-yl Me H H pyridazin-3-yl H H H H
1-methyl-indazol-6-yl Me H H pyridazin-3-yl H H H H
7-fluoro-1H-indazol- Me H H pyridazin-3-yl H H H H
6-yl
1H-indazol-6-yl Et H H pyridazin-3-yl H H H H
1H-indazol-6-yl Me H H 6- H H H H
methylpyridazin-
3-yl
1H-indazol-6-yl Me H H 6-dimethylamino- H H H H
pyridazin-3-yl
1H-indazol-6-yl Me H H 6-methylamino- H H H H
pyridazin-3-yl
1H-indazol-6-yl Me H H 6-amino- H H H H
pyridazin-3-yl
1H-indazol-6-yl Me H H 6-morpholin-4-yl- H H H H
pyridazin-3-yl
1H-indazol-6-yl Me H H 6-trifluoromethyl- H H H H
pyridazin-3-yl
1H-indazol-6-yl Me H H pyridazin-4-yl H H H H
1H-indazol-6-yl Me H H pyrazin-2-yl H H H H
1H-indazol-6-yl Me H H pyrimidin-2-yl H H H H
1H-indazol-6-yl Me H H pyrimidin-4-yl H H H H
1H-indazol-6-yl Me H H pyrimidin-5-yl H H H H
1H-indazol-6-yl Me H H 3,5-dimethyl- H H H H
isoxazol-4-yl
1H-indazol-6-yl Me H H thiazol-2-yl H H H H
1H-indazol-6-yl Me H H 5-methyl-thiazol- H H H H
2-yl
1H-indazol-6-yl Me H H cinnolin-3-yl H H H H
1H-indazol-6-yl Me H H phthalazin-1-yl H H H H
1H-indazol-6-yl Me H H quinoxalin-2-yl H H H H
1H-indazol-6-yl Me H H quinazolin-2-yl H H H H
1H-indazol-6-yl Me H H quinazolin-6-yl H H H H
1H-indazol-6-yl Me H H quinazolin-7-yl H H H H
1H-indazol-6-yl Me H H 3-oxo- H H H H
[1,2,4]triazolo[4,3-
a]pyridin-2-yl
1H-indazol-6-yl Me H H morpholin-4-yl H H H H
1-methyl-1H-indazol- Me H H morpholin-4-yl H H H H
6-yl
7-fluoro-1H-indazol- Me H H morpholin-4-yl H H H H
6-yl
1H-indazol-6-yl Me H H 2,6-dimethyl- H H H H
morpholin-4-yl
1H-indazol-6-yl Et H H morpholin-4-yl H H H H
1H-indazol-6-yl Me H F morpholin-4-yl H H H H
1H-indazol-6-yl Et H F morpholin-4-yl H H H H
1H-indazol-6-yl Me H H morpholin-4-yl F H H H
1H-indazol-6-yl Me H H morpholin-4-yl H F H H
1H-indazol-6-yl Me H OMe morpholin-4-yl H H H H
1H-indazol-6-yl Me H OH morpholin-4-yl H H H H
1H-indazol-6-yl Me H Me morpholin-4-yl H H H H
1H-indazol-6-yl Me H H morpholin-4-yl H H H OH
1H-indazol-6-yl Me H H morpholin-4-yl H H H Me
1H-indazol-6-yl Me H H piperidin-1-yl H H H H
1H-indazol-6-yl Me H H pyrrolidin-1-yl H H H H
1H-indazol-6-yl Me H H morpholin-4- H H H H
ylmethyl
1H-indazol-6-yl Me H H 1-methyl-1- H H H H
morpholin-4-yl-
ethyl
1H-indazol-6-yl Me H H 1-morpholin-4-yl- H H H H
cyclopropyl
1H-indazol-6-yl Me H H piperidin-1- H H H H
ylmethyl
1H-indazol-6-yl Me H H pyrrolidin-1- H H H H
ylmethyl
1H-indazol-6-yl Me H H CH2NMe2 H H H H
1H-indazol-6-yl Me H H CH2NHMe H H H H
1H-indazol-6-yl Me H H 2-oxo-2H-pyridin- H H H H
1-yl
1H-indazol-6-yl Me H H SO2CH3 H H H H
1H-indazol-6-yl Me H H CN H H H H
1H-indazol-6-yl Me H Me H H H H H
1-methyl-1H-indazol- Me H F H H H H H
6-yl
1-methyl-1H-indazol- Et H F H H H H H
6-yl
1-benzyl-1H-indazol- Me H H H H H H H
6-yl
(3-cyano-benzyl)-1H- Me H H H H H H H
indazol-6-yl
(2-cyano-benzyl)-1H- Me H H H H H H H
indazol-6-yl
1H-indazol-7-yl Me H H H H H H H

wherein the carbon atom designated * is in the R or S configuration. That is, the specific compounds herein include:

  • 4-(indazol-1-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-3-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-4-(1-methyl-1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(6-methoxy-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methoxy-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-chloro-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-methyl-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 1,2-dimethyl-4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 4-(1H-indazol-5-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,4-dimethyl-4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-fluoro-4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-chloro-4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(1H-indazol-5-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,7-dimethyl-4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 7-fluoro-2-methyl-4-(1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-1H-indazol-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indazol-5-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indazol-5-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;
  • 1-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-phthalazine;
  • 2-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinoxaline;
  • 2-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 6-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 7-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-quinazoline;
  • 2-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(morpholin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-methyl-1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 7-(2,6-dimethyl-morpholin-4-yl)-4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indazol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 8-fluoro-4-(1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-8-fluoro-4-(1H-indazol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 6-fluoro-4-(1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 5-fluoro-4-(1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-8-methoxy-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-8-ol;
  • 2,8-dimethyl-4-(1H-indazol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-ol;
  • 2,4-dimethyl-4-(1H-indazol-5-yl)-7-morpholin-4-yl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(piperidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(pyrrolidin-1-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-((morpholin-4-yl)methyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(1-methyl-1-morpholin-4-yl-ethyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-(1-morpholin-4-yl-cyclopropyl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-piperidin-1-ylmethyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-7-pyrrolidin-1-ylmethyl-1,2,3,4-tetrahydroisoquinoline;
  • [4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl]-dimethylamine;
  • [4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ylmethyl]-methylamine;
  • 1-(4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyridin-2-one;
  • 4-(1H-indazol-5-yl)-7-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
  • 4-(1H-indazol-5-yl)-2,8-dimethyl-1,2,3,4-tetrahydroisoquinoline;
  • 7-fluoro-2-methyl-4-(1-methyl-1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-7-fluoro-4-(1-methyl-1H-indazol-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1-benzyl-1H-indazol-5-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 3-[5-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-indazol-1-ylmethyl]-benzonitrile;
  • 2-[5-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-indazol-1-ylmethyl]-benzonitrile;
  • 4-(1H-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-4-(1-methyl-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 1,2-dimethyl-4-(1H-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-4-methyl-1,2,3,4-tetrahydroisoquinoline-4-ol;
  • 4-(1H-indazol-6-yl)-4-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,4-dimethyl-4-(1H-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-carbonitrile;
  • 4-fluoro-4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-chloro-4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol;
  • 4-(1H-indazol-6-yl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 2,7-dimethyl-4-(1H-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 7-fluoro-2-methyl-4-(1H-indazol-6-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-methyl-4-(1-methyl-1H-indazol-6-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(7-fluoro-1H-indazol-6-yl)-2-methyl-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 2-ethyl-4-(1H-indazol-6-yl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(6-methyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • [6-(4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-dimethylamine;
  • [6-(4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-yl]-methylamine;
  • 6-(4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-pyridazin-3-ylamine;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(6-morpholin-4-yl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(6-trifluoromethyl-pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(pyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(pyrazin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-7-(3,5-dimethyl-isoxazol-4-yl)-2-methyl-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 4-(1H-indazol-6-yl)-2-methyl-7-(5-methyl-thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline;
  • 3-(4-(1H-indazol-6-yl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-cinnoline;